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Everything you need to know about …

Everything you need to know about
Multiple Hereditary Exostoses…
A resource for MHE patients, their families,
and their health care providers

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  • 1. Everything you need to know about Multiple Hereditary Exostoses… A resource for MHE patients, their families, and their health care providers Updated and Revised October 1, 2005 Contributors: Harish Hosalkar, M.D. and John Dormans, M.D., Chief of Orthopedic Surgery, Children’s Hospital of Philadelphia; Sandra A. Darilek, MS, Department of Molecular and Human Genetics, Baylor College of Medicine and Jacqueline T. Hecht, PhD, Department of Pediatrics, University of Texas-Houston Medical School; Dror Paley, MD, Director, Rubin Institute for Advanced Orthopedics, Co-Director, International Center for Limb Lengthening, SinaiHospital of Baltimore; Wim Wuyts, PhD, Supervisor DNA Diagnostics, Departmentof Medical Genetics, University and University Hospital of Antwerp, Belgium; Elena McKeogh Spearing, MA, PT, DPT, PCS, Physical Therapy Manager, Children’s Hospital of Philadelphia; Richard B. Patt, MD, President and Chief Medical Officer of the Patt Center for Cancer Pain & Wellness, Houston, TX; Ronni Michelson, MSW, LSW; Elizabeth Munroz; Sarah Ziegler, Susan Wynn and Chele Zelina, The MHE Coalition The MHE Coalition 8838 Holly Lane Olmsted Falls, OH 44138 440-235-6325
  • 2. Table of Contents Chapter One: Orthopedics Section OneABC’s of MHE: Diagnostic Tools and How MHE Can Affect Each Part of the BodyContributors: Harish Hosalkar, MD, John Dormans, MD, Children’s Hospital ofPhiladelphia; Sarah Ziegler, Susan Wynn, Chele Zelina, The MHE Coalition Section TwoMultiple Exostoses and the Lower LimbReprinted from The MHE Coalition Newsletter No. 14, June 1, 2003Contributor: Dror Paley, MD, Director, Rubin Institute for Advanced Orthopedics; Co-Director, International Center for Limb Lengthening; Professor, University of MarylandSchool of Medicine Section ThreeMultiple Exostoses of the ForearmContributor: Dror Paley, MD, Director, Rubin Institute for Advanced Orthopedics; Co-Director, International Center for Limb Lengthening; Sinai Hospital of Baltimore Chapter Two: Genetics Section OneThe Genetics of Hereditary Multiple Exostosis (HME)Contributors: Sandra A. Darilek, MS, Department of Molecular and Human Genetics,Baylor College of Medicine, Houston, TX; Jacqueline T. Hecht, PhD, Department ofPediatrics, University of Texas-Houston Medical Center, Houston, TX
  • 3. Section TwoThe Genetics of Multiple Hereditary Exostoses - A Simplified ExplanationContributor: Wim Wuyts, Ph.D., Supervisor, DNA Diagnostics, Department of MedicalGenetics, University and University Hospital of Antwerp, Belgium Section ThreeGenetic Testing: Laboratories and Forms Chapter Three: Living with MHE Section OneThe Emotional Implications of Chronic Illness on MHE Patients and Their FamiliesReprinted from The MHE Coalition Newsletter No. 5, March 1, 2001Contributors: Ronni Michelson, MSW, LSW; Susan Wynn, The MHE Coalition; CathyLloyd Section TwoPhysical Therapy for Patients with Multiple Hereditary ExostosesContributor: Elena McKeogh Spearing, MA, PT, DPT, PCS, Physical Therapy Manager,Children’s Hospital of Philadelphia Section ThreeProducts and ideas to help make living with MHE a little easier…Reprinted from The MHE Coalition Newsletter No. 17, December 2004Contributor: Susan Wynn Section FourPreparing for your Next Medical AppointmentReprinted from The MHE Coalition Newsletter No. 16, June 2004 Section FiveMHE Surgery: Some helpful tips and advice from families who have been through itReprinted from The MHE Coalition Newsletter No. 10, June 1, 2002
  • 4. Chapter Four: MHE and Pain Section OneHereditary Multiple Exostoses and Pain, Abstract of Study Published in Journal ofPediatric OrthopaedicsContributors: Sandra Darilek, MS, Catherline Wicklund, MS, Diane Novy, PhD,Allison Scott, MD, Michael Gambello, MD, PhD, and Jacqueline Hecht, PhD Section TwoAmerican Pain Foundation – Pain Action GuideReprinted with permission of The American Pain Foundation; Appeared in TheMHE Coalition Newsletter 7, September 1, 2001 Section ThreeEvolving Views on Opioid Therapy for the Management of Chronic Pain. PainKillers (Analgesics): Panacea, Poison or Somewhere in BetweenReprinted from The MHE Coalition Newsletter No. 8, December 1, 2001Contributor: Richard B. Patt, MD Section FourReflex Sympathetic Dystrophy Syndrome: An OverviewReprinted from The MHE Coalition Newsletter No. 9, March 2002Contributor: Susan Wynn Chapter Five: MHE AND CHILDREN Section OneThe Bumpy Bone Survival GuideReprinted from MHE and Me, Section TwoThe MHE and Me Handbook: A Guide for Family Friends, Teachers andClassmatesReprinted from MHE and Me,
  • 5. Section ThreeCommon School Concerns for Students with MHESchool Needs Checklist for Kids with MHEReprinted from MHE and Me, Chapter Six: Chondrosarcoma Section OneA Patient’s Guide to ChondrosarcomaReprinted with permission from Elizabeth Munroz, Author and Webmaster of "A Patients Guide toChondrosarcoma Website); " ( Moderator, YahooChondrosarcoma Support Group; Founder and Webmaster of website outlining herpersonal story of MHE and Chondrosarcoma. Reprinted with permission of the author.
  • 6. Chapter One: Orthopedics Section OneABC’s of MHE: DiagnosticTools and How MHE Can Affect Each Part of the Body Contributors: Harish Hosalkar, MD, John Dormans, MD, Children’s Hospital of Philadelphia; Sarah Ziegler, Susan Wynn, Chele Zelina, The MHE Coalition
  • 7. The ABC’s of MHE Harish Hosalkar, MD., John Dormans, MD. Diagnostic Tools Important features of orthopedic exam: It is important to follow each step of the exam during every office assessment of MHE patients.• Patient should be comfortable with adequate exposure and well-lit surroundings (lest some important physical finding is missed).• It is important to assess how the patient moves about in the room before and during the examination as well as during various maneuvers. Balance, posture and gait pattern should also be checked.• General exam findings should look for any lumps and bumps that can be felt on any anatomical sites that can be easily palpated. Chest wall, abdominal and deep pelvic exam should be performed in all cases. Sessile or pedunculated nature of the bumps should be ascertained if possible.• General body habitus, including developmental milestones should be noted• It is important to note any obvious spinal asymmetry, deformities, trunk decompensation, and evidence of para-spinal muscle spasm or elevation suggestive of spinal lesions.• The patient’s height should be measured and monitored on subsequent visits. Individuals with MHE are frequently of short stature, with most having heights 0.5 to 1.0 SD below the mean. (The lesions tend to enlarge while the physes are open proportionate to the overall growth of the patient, and the growth of the osteochondromas usually ceases at skeletal maturity).• It is essential to perform and document a thorough neurologic exam. Asymmetric abdominal reflex is a subtle sign of spinal pathology and may be associated with spinal cord compression. Motor, sensory and reflex testing should be performed and recorded.• Any discrepancies in limb lengths should be noted and evaluated as femoral, tibial or both.• Arm, forearm, thigh and leg girths should be recorded especially so when an obvious difference is noted on clinical exam.• Any deformities should be noted and recorded. The most common deformities seen in MHE include short stature, limb-length discrepancies, valgus deformities of the knee and ankle, asymmetry of the pectoral and pelvic girdles, bowing of the radius with ulnar deviation of the wrist, and subluxation of the radial head.• The range of motion of all joints, their stability, and any evidence of hyperlaxity, should also be noted in all cases.• Distal vascular and neurological status (motor, sensory and reflex) should be evaluated and recorded. This includes checking of pulse in hands and feet as well as sensations. Chapter One 1 Section One
  • 8. Frequency of Follow-up Children should be followed up at 6-9 month intervals and sooner if there are any red flags in terms of sudden increase in size of the bump, pain, tingling, numbness, weakness, visible and progressive limp, limb deformities and length discrepancies It is important to keep a regular follow-up of all cases even after skeletal maturity. Most patients have increased awareness of all the red flags to be watched for by this time and hence can keep a personal lookout for the same. A thorough exam can be performed by the clinician (including measurements) during the office visit. Radiographs should be repeated only when the bumps are symptomatic or growing.Note: Your child’s orthopaedist may recommend follow-up at different intervals,sometimes every 3 months, sometimes a year or more, and can explain why that timeframe is indicated.Characterization of Lesions:Location: Whether the tumor is located in the limb bones, chest wall or ribs, skull, or anyother sites in the body. 1. Pain: Is the lesion associated with pain? If yes: • Intensity: Can be assessed and documented in a lot of ways. i. On a pain scale of 1 to 10. ii. The MHE and Me Website now features the Bumpy Bone Tracker, Pain Tracker, Pain Tracker for Little Kids, and a Pain Diary, all of which can be used as a tool to discuss pain with a child during an examination • Quality: i. Do you experience pain on and off (intermittently) throughout the day, or all the time (constantly)? ii. Does the pain occur at specific times, or with specific activities (ex. Upon waking in the morning, when walking, etc.) iii. Is pain interfering with your general activities? iv. Do you need to use special accommodations at work or school? v. Is pain affecting your mood? vi. Do you take medications for pain, or use other treatments (i.e. heat, ice, rest). If so, are these treatments effective? vii. Tumor pain is often unrelenting, progressive, and often present during the night. viii. Is there any shooting pain? (Suggestive of nerve compression) • Radiation: Pain radiating to upper or lower extremities or complaints of numbness, tingling or weakness suggest neurologic compression and requires appropriate workup.Chapter One 2 Section One
  • 9. 2. Onset: • How was the tumor noticed? • Was there any history of trauma? • When did the pain actually start? 3. Duration: • What has been the duration of this new lesion? • How long have the other lesions been around? 5. Progress: Whether the exostosis has remained the same, grown larger, or gotten smaller? 6. Associated symptomatology: a. Gait and posture disturbances (especially during follow-up of skull or spinal lesions and in cases of limb-length discrepancies and deformities). b. Any specific history of backpain. If yes, its complete characterization. c. Change in bladder or bowel habits (for evidence of spinal lesions causing cord compression) d. Gynecologic function alterations in girls with pelvic lesions. e. Scoliosis may be associated with spinal lesions and may need to be monitored. f. Night pain if present is a worrisome symptom and needs complete evaluation. Night pain is different than chronic pain in that the pain is not constant and characteristically wakes the patient from sound sleep. Chronic pain on the other hand is persistent and would interfere with the sleep pattern by making the patient restless. Chronic night pain is especially common in MHE cases where the location of the bump may cause pressure on the exostoses when lying down. Soft beds, air cushions, lateral positioning and frequent turning may prove to be helpful in these cases. g. Neurologic symptoms may be associated spinal or skull lesions. More commonly, local compression of peripheral nerves due to expanding lesions is encountered in arms and legs. In addition, several cases of Reflex Sympathetic Dystrophy (RSD) following MHE surgeries to knees and wrists have been noted. Many patients also experience other nerve- related symptoms following surgery, including long-lasting pain and sensitivity around surgical sites long after incisions have healed. h. Bursa formation and resulting bursitis may occur as a result of the exostoses and should be recorded. A bursa is a fibrous sac lined with synovial membrane and filled with synovial fluid and is found. The function of a bursa is to decrease friction between two surfaces that move in different directions. Therefore, you tend to find bursae at points where muscles, ligaments, and tendons glide over bones. These bursae can be either anatomical (present normally) or may be developmental (when the situation demands). The bursae can be thought of as a zip lock bag with a small amount of oil and no air inside. In the normal state, this would provide a slippery surface that would have almost no friction. A problem arises when a bursa becomes inflamed. It loses its gliding capabilities, and becomes more and more irritated when it is moved. Bursitis can either result from a repetitive movement or due to prolonged or excessive pressure.Chapter One 3 Section One
  • 10. Note from The MHE Coalition: Children who have been experiencing MHE-related pain may be hesitant to share this information with their doctors, fearing that the doctor will recommend surgery. It is not unusual for children to try to minimize their symptoms. We advise families to use the pain tracker tools available to keep an ongoing record between check- ups. It is also important for both parents and physicians to let children know that pain does not necessarily mean surgery, but that it is important to let the doctor know about symptoms they have been experiencing.Diagnostic work-upPhysical examination.A thorough physical examination of the patient is extremely important in the assessmentof MHE patients.RadiographsHigh quality plain radiographs (X-rays) (anteroposterior and lateral views) should beordered in cases presenting with exostoses. Standing postero-anterior and lateral views ofthe entire spine on a three-foot cassette should be ordered when spinal lesions aresuspected. Special views like tangential views of the scapula may need to be ordered insome cases. Plain films help to localize the lesion and give a fairly good idea about itssize and dimensions in 2 planes. Also scanograms help to assess the extent of limb-length discrepancy and its localization. Oblique views of the spine and special skullviews may be ordered in suspected cases.Advanced ImagingRadionucleide bone scan is sensitive to pathologies causing increased bone activitieswithin the skeleton. In combination with SPECT (single photon emission computedtomography), it gives excellent localization of the area of increased uptake. This isextremely useful in MHE to locate multiple lesions, especially those that are situated indeeper areas not amenable to clinical palpation. Further imaging if required, can then befocused. Thallium and PET (positron emission Tomography) scans are also modalitiesthat can help define the tumor metastasis especially in those rare cases of malignantdegeneration.Computed Tomography (CT)CT scans are useful in visualizing the bony architecture particularly as an adjunct to plainradiographs or bone scans. Thin slice CT cuts may be necessary in small lesions. Twoand three-dimensional reconstructions are possible and add to the information. Rarely theCT may be combined with the myelogram to effectively delineate the size of the lesionespecially for intraspinal lesions.Chapter One 4 Section One
  • 11. Magnetic Resonance Imaging (MRI)This is an excellent modality for defining the spinal cord, nerve roots, soft tissuestructures and cartilage. Cortical bone is not seen as well as compared with CT.Cartilage caps of the exostoses and their compression effects on soft-tissues, nerves andadjacent vessels can be very well delineated. It is a study of choice in suspected cases ofmalignant transformation. MRI studies must be reserved for those cases in which clinicalsigns and symptoms deem them appropriate. Clinicians must make a point tocommunicate clinical information and suspected differential diagnosis to the radiologists.Other Diagnostic ToolsUltrasoundMay be necessary to diagnose compression of arteries. The principle for ultrasound, orultrasonography, is the same as for underwater sonar or echo sounding. An apparatussends an ultrasonic wave through the body at a speed of about 1,500 meters per second.At the interface between two types of tissue, the wave will be refracted or ‘broken up’,and part of the wave will be reflected back and detected by the apparatus. The rest of theultrasonic wave continues deeper into the body, and is reflected as an echo from thesurface of tissues lying further inside the body. How much is reflected depends on thedensities of the respective tissues, and thus the speed of the sound wave as it passesthrough them. The time taken for the reflected wave to return indicates how deep thetissue lies within the body. In this way, one obtains a picture of the relative locations ofthe tissues in the body, in the same way that one may visualize the contours of a school offish with sonar. An ultrasound can help ascertain the status of the blood flow through thearteries as well and is therefore important for assessment of suspected compression.EMG (Electromyography, myogram)May be necessary in cases of suspected nerve damageWhat is EMGElectromyography is a test that measures muscle response to nervous stimulation(electrical activity within muscle fibers).How the test is performedA needle electrode is inserted through the skin into the muscle. The electrical activitydetected by this electrode is displayed on a monitor (and may be heard audibly through aspeaker). Several electrodes may need to be placed at various locations to obtain anaccurate study.After placement of the electrode(s), you may be asked to contract themuscle (for example, by bending your arm). The presence, size, and shape of the waveform (the action potential) produced on the monitor provide information about the abilityof the muscle to respond when the nerves are stimulated.Each muscle fiber that contracts will produce an action potential, and the size of themuscle fiber affects the rate (frequency) and size (amplitude) of the action potentials.A nerve conduction velocity test is often done at the same time as an EMG.Chapter One 5 Section One
  • 12. Why the test is performedEMG is most often used when people have symptoms of weakness and examinationshows impaired muscle strength. It can help to differentiate primary muscle conditionsfrom muscle weakness caused by neurologic disorders.EMG can be used to differentiate between true weakness and reduced use due to pain orlack of motivation.HistologyClinical examination and Imaging findings can help establishing the diagnosis in mostcases. Biopsy should be performed when a malignant change is suspected.Laboratory evaluationGenetic linkages to MHE have been documented which form the basis of genetic testing.Test methods:Sequence analysis of the EXT1 and EXT2 genes are offered as separate tests. Usinggenomic DNA obtained from buccal (cheek) swabs or blood (5cc in EDTA), testing ofEXT1 proceeds by bi-directional sequence analysis of all 11 coding exons. The EXT2gene consists of 15 exons, and all coding exons (2-15) are sequenced in the analysis.Test sensitivity:In patients with MHE, mutations are found in approximately 80% of individuals. Ofthose in whom mutations are identified, 70% of the mutations are found in the EXT1gene and the remaining 30% in the EXT2 gene. Thus, the method used to screen theEXT1 is expected to identify approximately 60% of mutations in MHE. In individualswho are found to be negative on analysis of the EXT1 gene, screening of the EXT2 genewill identify the molecular basis of the disease in a further 25% of affected individuals.To date, there are no known distinguishing features within the clinical diagnosis of MHEknown to predict which gene is more likely to have a mutation. Multiple exostoses can beassociated with contiguous deletion syndromes, which are not detected with thesemethods.Chapter One 6 Section One
  • 13. How MHE Can Affect Each Part of the BodyMHE usually manifests during early childhood more commonly with several knobby,hard, subcutaneous protuberances near the joints.The likelihood of involvement of various anatomical sites as observed in a large series isas follows:Anatomical location Percentage involvementDistal femur 70Proximal tibia 70Proximal fibula 30Proximal Humerus 50Scapula 40Ribs 40Distal radius and ulna 30Proximal femur 30Phalanges 30Distal fibula 25Distal tibia 20Bones of the foot 10-25The SkullLesions in the skull, although reported are extremely rare. Mandibular osteochondromas,typically of the condyle, skull wall lesions and even intracranial lesions have beenreported.Affects of MHE on SkullExostoses can cause problems if they compress or entrap cranial nerves or cause extrinsiccompression on the brain. Effects can range from bumpy external lesions that causecosmetic problems, compression of adjacent structures, cranial nerve involvement andeven focal neurological deficits due to compression. Even seizures are likely due tointracranial lesions.Diagnostic ProceduresThe orthopedist will manually feel for exostoses along the outer table of the skull, checkmovements of the mandible and also of the upper cervical spine. The orthopedist willalso check cranial nerve function and perform a thorough neurological evaluation. X-raysor other imaging tests including CT and MRI may be ordered.Possible Treatment Options Minor lesions on the outer table of the skull that are flat can sometimes be closelyobserved.Chapter One 7 Section One
  • 14. Bigger lesions on the skull, mandibular lesions causing TM joint instability, andintracranial lesions causing pressure signs may need to be removed by neurosurgicalintervention. Upper cervical spinal tumors, especially of the atlanto-occipital region may be dealtwith by orthopedists. Decompression and or stabilization may be performed as required.What Parents Should Watch Out For Pain. Is your child experiencing pain from exostoses? Visible lumps on the face or skull. Any symptoms of tingling, numbness, weakness in the hands or legs suggestive offocal deficits. Episodes of seizures or findings of cranial nerve involvement like altered smell,taste, ringing in ears etc. Problems in chewing, restricted motion of the jawbone or instability of the mandible. Parents can ask dentists and orthodontists to be on the lookout for signs suggestive ofjawbone instability or joint involvement during their office visits especially insymptomatic cases.SpineThe spine extends from the base of the skull to the tailbone. Spinal exostoses are rare(Figure 1). Spinal cord impingement is also a rare, but documented, complication ofMHE. Cervical, thoracic or lumbar region can be affected. Scoliosis secondary to spinalosteochondromas and instability has been reported.Affects of MHE on the Spine:This section of the body is not commonly involved with MHE. Involvement of isolatedvertebrae has been noted. Affects can range from instability to neural root or cordcompression that can manifest as tingling, numbness or weakness in the involved roots oreven major neurological deficits like paraparesis or quadriparesis in untreated cases.Rarely compression effects in the form of dysphagia, intestinal obstruction or urinarysymptoms may occur.Diagnostic Procedures:With any of the red flags mentioned earlier, the orthopedist will perform a thoroughspinal and neurological evaluation. Plain x-rays of the spine and if required, advancedimaging may be performed. The presences and extent of the lesion are best delineatedwith CT, while MRI of the spinal cord demonstrates the area of spinal cord impingement.Chapter One 8 Section One
  • 15. In rare cases of peripheral nerve compression electromyography may be performed tocheck status of the nerve.Possible Treatment Options: Minor lesions not causing compressive symptoms or neurologic manifestations maybe kept under close observation. Progressive scoliosis and spinal instability may need to be treated with surgicalstabilization involving spinal fusion.What Parents Should Watch Out For: Any red flags in terms of tingling, numbness, weakness, night pain or bladder andbowel changes and get them evaluated. Any deformity in the spine or evidence of shoulder or pelvic imbalance. Gait or posture disturbances. Remember that gait and posture disturbances can becaused by hip or leg exostoses as well (due to either limb-length discrepancy ordeformity) and do not necessarily mean tumors in the spine. In any case evaluation by aclinician is important.Ribs and SternumAffects of MHE on the ribs and sternumThe typically flat bones of the ribs are prone to effects of MHE, with approximately 40%of MHE patients having rib involvement. Prominent chest wall lesions are commonalthough intrathoracic lesions including rare presentations like spontaneous hemothorax(build-up of blood and fluid in the chest cavity) as a result of rib exostoses have beendescribed. Typically, these lesions create issues of cosmesis due to their obviousvisibility. Other symptoms may include shortness of breath and other breathingdifficulties, pain when taking a deep breath, when walking or exercising, or pain fromexostoses “catching”.Diagnostic ProceduresThe orthopedist will probably manually feel for exostoses along the chest wall and theribcage. Size and extent of the lesions are noted. A thorough pulmonary evaluation iswarranted in all cases when specific symptoms of cough, chest pain or breathingproblems are encountered. X-rays or other imaging tests may be ordered.Possible Treatment Options: Minor bumps can sometimes be kept under observation. Cosmetic problems, rapid increase in size, large size, and signs of compression aresome indications for early removal. Consult may be required with specialists:Pulmonary: when there are severe breathing difficulties with increasing chest pain.Thoracic surgeons: when intrathoracic (within the chest wall) exostoses may need to beexcised.What Parents Should Watch Out For: Breathing difficulties, shortness of breath Pain when taking deep breath.Chapter One 9 Section One
  • 16. Shoulder girdleThe scapula is a fairly common site (40%) of involvement in MHE. The lesions may belocated on the anterior or posterior aspect of the scapula. Anterior scapular lesions maylead to discomfort during scapulothoracic motion. Winging of the scapula due toexostoses has been described. Clavicle (collar bone) involvement has also been described(5% cases).What is winging?The scapula (also known as shoulder blade) is a triangular flat bone that is located in theupper back and takes part in forming the shoulder joint. The scapula usually lies flat onthe chest wall without any prominence. Winging of the scapula is a phenomenon when apart of the scapula including the inferior angle becomes prominent either at rest or duringmovements. The two most common causes for this are1. Exostosis on the inner (chest wall) aspect of the scapula.2. Damage to the nerve (long thoracic) causing weakness or paralysis of muscles(serratus anterior) attached to the scapula.Diagnostic ProceduresThe orthopedist will probably manually feel for exostoses along the outer aspect of theshoulder blade. Some limited areas of the inner aspect are amenable to clinicalexamination. Range and feel of the scapulothoracic motion is helpful in clinicalassessment. It is important to check individual groups of scapular muscles to rule outnerve compression leading to winging of scapula. X-rays (including special tangentialviews of the scapula) or other imaging tests may be ordered.Possible Treatment Options Both outer aspect lesions and inner ones may need excision in symptomatic cases.Smaller lesions on outer aspect amenable to clinical palpation may be observed withregular clinical follow-up.What Parents Should Watch Out For: Crunching or crackling sound when moving that area Pain Tingling, numbness Note from The MHE Coalition: Exostoses in the shoulder girdle (collarbone (clavicle) and shoulder blade can impact a child’s ability to raise his/her arm in class, write on a blackboard, participate in certain sports, or wear a backpack. In addition, adolescent girls (and women) may be unable to wear a bra because of pressure not only on shoulder girdle exostoses but also on rib exostoses.Arms Upper Arm (Humerus) Elbow Forearm (Radius and Ulna)Chapter One 10 Section One
  • 17. WristsThe arm bone is called the humerus while the forearm bones are the radius (curved bone)and the ulna (straighter bone of the two).Osteochondromas of the arm are often readily felt but rarely cause neurologicdysfunction (Figure 2). Osteochondromas of the upper extremities frequently causeforearm deformities. The prevalence of such deformities has been reported to be as highas 40-60%. Disproportionate ulnar shortening with relative radial overgrowth has beenfrequently described and may result in radial bowing. Subluxation or dislocation of theradial head is well-described sequelae in the context of these deformities.The length of forearm bones inversely correlates with the size of the exostoses. Thus, thelarger the exostoses and the greater the number of exostoses, the shorter the involvedbone. Moreover, lesions with sessile rather than pedunculated morphology have beenassociated with more significant shortening and deformity. Thus, the skeletal growthdisturbance observed in MHE is a local effect of benign growth. Exostoses in the forearmare known to involve both the radius and the ulna. Since movements of the forearm(pronation and supination) are dependant on the radius moving in an arc of motionaround the ulna, mobility may be restricted depending upon the severity of presentation.Also the lower end radius exostoses can lead to compression of the median nerve (in aclosed space at the level of the wrist called the carpal tunnel) and present with weakness,tingling and numbness in the hand. Exostoses in the carpal bones can seriously hamperthe wrist motion and cause pain.Complete dislocation of the radial head is a serious progression of forearm deformity andcan result in pain, instability, and decreased motion at the elbow. Surgical interventionshould be considered to prevent this from occurring. When symptomatic, this can betreated in older patients with resection of the radial head.Diagnostic Procedures:The orthopedist will clinically feel for exostoses along the arm, elbow and forearm, andcheck range of motion (“ROM”) by moving the arm in different directions. Theorthopedist will also check measurements on each arm and forearm to see if there is adifference. X-rays or other imaging tests may be ordered.Possible Treatment Options:Indications for surgical treatment include painful lesions, an increasing radial articularangle, progressive ulnar shortening, excessive carpal slip, loss of pronation, and increasedradial bowing with subluxation or dislocation of the radial headChapter One 11 Section One
  • 18. Minor lesions can sometimes be observed with careful follow up. Bowing and some length discrepancies and be treated with a surgical procedurecalled “stapling,” where surgical staples are inserted into the growth plate of the bonegrowing faster than the other. This will hopefully give the slower growing bone thechance to “catch up” and the forearm will straighten over time. Limb Lengthening with a fixator. (See Section on Fixators) Resection of the radial head Excision of exostoses Osteotomy Epiphysiodesis Non-surgical measures for treatment of soft-tissue compression, irritation orinflammation (anti-inflammatories, heat, rest, etc.) Adaptive devices to aid those with shortened forearms, such as grippers, long-handled sock aides, etc.What Parents Should Watch Out For: Any red flags in terms of sudden increase in size of swelling, pain, nervecompression, tingling, numbness, or weakness. Possibility of exostoses irritating or catching on overlying tissue, such as muscles,tendons, ligaments, or compressing nerves. Loss of range of motion Pain Difficulty and/or pain when raising arm(s), lifting, carryingHands and FingersHand involvement in MHE is common. Fogel et al. observed metacarpal involvementand phalangeal involvement in 69% and 68%, respectively, in their series of 51 patients.In their series of 63 patients, Cates and Burgess found that patients with MHE fall intotwo groups: those with no hand involvement and those with substantial hand involvementaveraging 11.6 lesions per hand. They documented involvement of the ulnar metacarpalsand proximal phalanges most commonly with the thumb and distal phalanges beingaffected less frequently. While exostoses of the hand resulted in shortening of themetacarpals and phalanges, brachydactyly was also observed in the absence of exostoses.Diagnostic Procedures:The orthopedist will manually feel for exostoses in the hands and check range of motion(“ROM”) in different directions. X-rays or other imaging tests may be ordered.Possible Treatment Options: Isolated lesions growing rapidly, or interfering with the smooth motion of tendons orjoint motion may need to be excised. Multiple surgeries for small, insignificant lesions isusually not advocated. Occupational therapy, physical therapy Use of pencil grips, laptop computers, and other adaptive devicesWhat Parents Should Watch Out For: Complaints of pain when writingChapter One 12 Section One
  • 19. Some children will not complain of pain, but will have poor penmanship, writeslowly, avoid writing, etc. Parents should also observe how the child holds writing andeating utensils. Difficulty in rotating hand(s),Pelvic Girdle (Hips and Pelvis)Osteochondromas of the proximal femur (Figure 3) may lead to progressive hipdysplasia. There have been reported cases of acetabular dysplasia with subluxation of thehip in patients with MHE. This results from exostoses located within or about theacetabulum that may interfere with normal articulation.Pelvic lesions (Figures 4 and 5) may be found on both the inner as well as outer aspect ofthe pelvic blades. Large lesions may cause signs of compression, both vascular andneurological. There have also been reports of exostoses interfering with normalpregnancy and leading to a higher rate of Cesarean sections.Diagnostic ProceduresManual palpation is sometimes very difficult in these deep lesions. The orthopedist willcheck range of motion (“ROM”) by manipulating (moving) the leg in different directions.The orthopedist will also check measurements on each leg to see if there is a difference inlimb lengths. X-rays or other imaging tests may be ordered.Possible Treatment Options Minor length discrepancies can sometimes be effectively treated with the use oforthotics (specially made shoes or lifts that will equalize leg length).Chapter One 13 Section One
  • 20. Bowing and some limb length discrepancies can be treated with a surgical procedurecalled “stapling,” where surgical staples are inserted into the growth plate of the leg bonegrowing faster than the other. This will hopefully give the slower growing bone thechance to “catch up” and the limb will straighten over time. Limb Lengthening with a Fixator. (See Section on Fixators) Pelvic lesions of concern may need to be surgically excised. Osteotomies. Hip replacement.What Parents Should Watch Out For Limping Pain in hips, back, legs Pain, discomfort, difficulty in sitting Inability to sit “tailor” style Stiffness in hips and/or legs after sitting Pain and fatigue from walkingLegs and Knees Femur Knees Lower Leg (Tibia and Fibula)The likelihood of involvement near the knee (figures 6 & 7) in at least one of the threelocations is approximately 94%.A clinically significant inequality of 2cm or greater has been reported with a prevalenceranging from 10-50%. Shortening can occur in the femur and/or the tibia; the femur isaffected approximately twice as commonly as the tibia. Surgical treatment withappropriately timed epiphysiodesis has been satisfactorily employed in growing patients.In addition to limb-length discrepancies, a number of lower extremity deformities havebeen documented. Since the disorder involves the most rapidly growing ends of the longbones, the distal femur is among the most commonly involved sites and 70-98% ofpatients with MHE have lesions. Coxa valga has been reported in up to 25%; lesions ofthe proximal femur have been reported in 30-90% of patients with MHE. Femoralanteversion and valgus have been associated with exostoses located in proximity to thelesser trochanter.Genu Valgum or Knock-knee deformities are found in 8-33% of patients with MHE. Genuvalgum is defined as a mechanical malalignment of the lower limb when the knees knockChapter One 14 Section One
  • 21. against each other and the legs are pointed away from the body. Although distal femoralinvolvement is common, the majority of cases of angular limb deformities are due mostlyto lesions of the tibia and fibula (Figures 8,9 & 10), which occur in 70-98% and 30-97%of cases, respectively. The fibula has been found by Nawata et al. to be shorteneddisproportionately as compared to the tibia, and this is likely responsible for theconsistent valgus direction of the deformity. Genu varum or Bowlegs may also occur insome cases. This is defined as a mechanical malalignment of the lower limb when theknees drift away from the body and the legs are bowed and close together.Diagnostic ProceduresThe orthopedist will probably manually feel for exostoses along the leg, and check rangeof motion (“ROM”) by manipulating (moving) the leg in different directions. Theorthopedist will also check measurements on each leg to see if there is a difference. X-rays or other imaging tests may be ordered.Possible Treatment Options Minor length discrepancies can sometimes be effectively treated with the use oforthotics (specially made shoes or lifts that will equalize leg length). Bowing and some limb length discrepancies and be treated with a surgical procedurecalled “stapling,” where surgical staples are inserted into the growth plate of the leg bonegrowing faster than the other. This will hopefully give the slower growing bone thechance to “catch up” and the limb will straighten over time. Limb Lengthening with a Fixator. (See Section on Fixators) Excision of exostoses OsteotomyWhat Parents Should Watch Out For Any red flags in terms of sudden increase in size of swelling, pain, nervecompression, tingling, numbness, or weakness. Possibility of exostoses irritating or catching on overlying tissue, such as muscles,tendons, ligaments, or compressing nerves. Leg cramps, bluish color, difference in skin temperature may indicate compressionof an artery (most often the popliteal artery, located behind the knee). Compression of the peroneal nerve, which runs along the outside of the leg, cancause a condition known as “drop foot”, in which the foot cannot voluntarily be flexedup. Compression can be caused by exostoses growth, or as a complication of surgery. Limping, pain when walking Bowing of leg(s) Exostoses on inside of legs bumping into each other Exostoses interfering with normal movements, either by blocking movement or bycausing pain (bending, sitting, walking up or down stairs) Pain and fatigue when walking Gait problems (awkwardness, limping, slow movements, etc.)Chapter One 15 Section One
  • 22. Notes from The MHE Coalition: A good way to track possible bowing in your child’s legs is to take a photo of your child dressed in shorts, standing straight with back to wall, legs together. Every few months take another photo of your child in the same position, and date and keep these photos to show your child’s doctor. You can even have your child hold a sign with the date you take the picture (written dark enough to be picked up by the camera!).AnklesValgus deformity of the ankle is also common in patients with MHE and is observed in45-54% of patients in most series. This valgus deformity can be attributed to multiplefactors including shortening of the fibula relative to the tibia. A resulting obliquity of thedistal tibial epiphysis and medial subluxation of the talus can also be associated with thisdeformity, while developmental obliquity of the superior talar articular surface mayprovide partial compensation.Diagnostic Procedures:The orthopaedist will probably manually feel for exostoses along the leg, and check rangeof motion (“ROM”) by manipulating (moving) the leg in different directions. Theorthopaedist will also check measurements on each leg to see if there is a difference. X-rays or other imaging tests may be ordered.Possible Treatment Options: Minor length discrepancies can sometimes be effectively treated with the use oforthotics (specially made shoes or lifts that will equalize leg length). Bowing and some limb length discrepancies and be treated with a surgical procedurecalled “stapling,” where surgical staples are inserted into the growth plate of the leg bonegrowing faster than the other. This will hopefully give the slower growing bone thechance to “catch up” and the limb will straighten over time. In more advanced cases, excision of exostoses with early medial hemiepiphysealstapling of the tibia in conjuction with exostosis excision can correct a valgus deformityat the ankle of 15° or greater associated with limited shortening of the fibula. Fibular lengthening has been used effectively for severe valgus deformity with moresignificant fibular shortening, (i.e. when the distal fibular physis is located proximal tothe distal tibial physis). Supramalleolar osteotomy of the tibia has also been used effectively to treat severevalgus ankle deformity. Growth of exostoses can also result in tibiofibular diastasis that can be treated withearly excision of the lesions.What Parents Should Watch Out For: Limping, pain when walking Recurrent falls and instability while walking on uneven surfaces.Chapter One 16 Section One
  • 23. Feet and ToesOsteochondromas may occur in the tarsal and carpal bones, however they are often lessapparent. Relative shortening of the metatarsals, metacarpals, and phalanges may benoted.Diagnostic ProceduresPlain radiographs are probably more useful in defining the extent of involvement of thesmall bones of the feet in MHE. Other imaging studies may be ordered as and whenrequired.Possible Treatment Options Large bumps can be surgically excised when symptomatic Deformities of the foot (like hallux valgus) may be corrected by stapling of thegrowing epiphysis in younger children or by surgical osteotomy in older patients.What Parents Should Watch Out For Compression of the peroneal nerve, which runs along the outside of the leg, cancause a condition known as “drop foot”, in which the foot cannot voluntarily be flexedup. Compression can be caused by exostoses growth, or as a complication of surgery. Note from The MHE Coalition: Parents should know that finding shoes for children affected with ankle and/or foot exostoses can be challenging. Shoes must be found that do not cut into or press on exostoses. In some cases, they must be made specially for the child. In addition, some children will require lifts to help equalize a limb length discrepancy. Children who have exostoses on the bottom of their heel can sometimes benefit from gel cushions that are sold in drug/grocery stores. In addition, many children and teens will have difficulty tying shoes due to affected hands, shortened forearms, etc., and may need shoes with Velcro or shoes that slip on.In generalWhat Parents Should Watch Out For If your child is limping, check to see if it is due to an injury, or is something that isoccurring and continuing without obvious reason. Limping may signal a limb lengthdiscrepancy or other problem. Bowing of one or both legs Mobility problems. Is your child experiencing pain when walking or running? Pain. Is your child experiencing pain from exostoses that bump each other? Is yourchild experiencing pain during certain activities, or pain at night. If so, keep a pain diary. Any red flags in terms of sudden increase in size of swelling, pain, nervecompression, tingling, numbness, or weakness.Chapter One 17 Section One
  • 24. The MHE Coalition and its member organization, MHE and Me, offers theFollowing Patient Support Information: “Tips for When Your Child Needs Surgery” The Bumpy Bone Tracker The Bumpy Bone Pain Tracker The Bumpy Bone Pain Tracker for Little Kids The Bumpy Bone Pain Diary The MHE and Me Handbook: A Guide for Families, Friends, Teachers and Classmates School Needs Checklist for Kids with MHE Common School Concerns for Kids with MHEWhat Adults Should Be Aware Of: Sudden growth in an existing exostosis and pain can be symptomatic of a malignanttransformation. It is smart to check out any changes with your orthopaedist. However, itis important to remember that chondrosarcoma is rare. Years of wear and tear on joints can result in chronic pain. There is also thepossibility of exostoses irritating or catching on overlying tissue, such as muscles,tendons, ligaments, or compressing nerves. Possible Treatment Options for thesecommon problems, include pain medications, physical therapy (including stretching,strengthening and modalities), heat, rest, bracing (supportive orthosis acting as loadsharing devices) etc.Chapter One 18 Section One
  • 25. Glossary of terms and procedures:Synonyms of multiple exostoses: A number of synonyms have been used forthis disorder including osteochondromatosis, multiple hereditaryosteochondromata, multiple congenital osteochondromata, diaphysealaclasis, chondral osteogenic dysplasia of direction, chondral osteoma,deforming chondrodysplasia, dyschondroplasia, exostosing disease,exostotic dysplasia, hereditary deforming chondrodysplasia, multipleosteomatoses, and osteogenic disease.Anterior: Situated in the front; forward part of an organ or limbBall and socket joints: Movable (synovial) joints, such as hips and shoulders, that allowa wide range of movement.Bilateral: having two sides or pertaining to both sides.Biopsy: Take a piece of the lesion to study the histological characteristics.Cartilage: Form of connective tissue, more elastic than bone, which makes up parts ofthe skeleton and covers joint surfaces of bones.Coxa-valga: When the thighbones are drawn farther apart from the midline due to anincrease in the neck-shaft angle of the femur.Coxa-vara: When the thighbones are drawn closer to the midline due to a decrease in theneck-shaft angle of the femur.Dislocation: When the normal articulating joint surfaces have lost total contact.Distal: Away from the midline or the beginning of a body structure (the distal end of thehumerus forms part of the elbow).Epiphysiodesis: To surgically stop the growth of the growing end of the bone eithertemporarily or permanently.Excision: To surgically remove the lesion.Genu-valgum: Knock-knees.Genu-varum: Bowlegs.Hinge joints: movable joints, such as knees and elbows, that allow movement in onedirection.Limb-lengthening: Process of increasing the length of bones using one of the variousdevices.Chapter One 19 Section One
  • 26. LLD: Limb-length discrepancy- difference in limb lengths.Medial: Pertaining to the middle or toward the midline.MHE: An autosomal-dominant disorder manifested by multiple osteochondromas andfrequently associated with characteristic skeletal deformities.Osteochondromas: Cartilage capped tumors found commonly at rapidly growing ends ofbones.Osteotomy: The surgical division or sectioning of a bone.Pedunculated: Lesion with a stalk connecting it to the main bone.Posterior: Situated in the back; back part of an organ or limbProximal: Near the midline or beginning of a body structure (the proximal end of thehumerus forms part of the shoulder).Sessile: Lesion without a stalk connecting it to the main bone.Stapling: Process of insertion of a mechanical device (staple) following surgicalintervention.Subluxation: When the joint surfaces are still facing each other but not totally in contact.Chapter One 20 Section One
  • 27. Chapter One: Orthopedics Section TwoMultiple Exostoses and the Lower Limb Contributor: Dror Paley, MD, Director, Rubin Institute forAdvanced Orthopedics, Co-Director, International Center for Limb Lengthening at Sinai Hospital of Baltimore
  • 28. Multiple Exostoses and the Lower Limb Dror Paley, MDOsteochondromasThere are a variety of problems related to the exostoses of Hereditary MultipleOsteochondromas. The majority of these problems relate to bothersome bony protrusionswith their affect on surrounding joints, muscles, tendons, nerves, blood vessels and skin.Osteochondromas can also affect growth plates and lead to limb deformities and lengthdiscrepancies. The focus of this article will be on the limb deformities and discrepanciessecondary to the multiple osteochondromas.Lower LimbOsteochondromas are believed to bud off the growth plates. The cartilaginous cap of theosteochondroma has the same structure as the growth plate. It grows in length and widthin the same fashion as a growth plate leads to growth in length and width of the end of abone. For reasons unknown some osteochondromas tether the growth of the growth platewhen they bud off. This can lead to asymmetric growth (less growth on theosteochondroma side and more growth on the opposite side of the growth plate) andconsequently limb deformity. This tethering effect can also decrease overall limb growthleading to a shorter final limb length than expected. If the opposite lower limb is not asaffected then the result is a lower limb length discrepancy (LLD). Although both lowerlimbs often appear to be equally affected by osteochondromas, LLD is not uncommonindicating that one side is more tethered at the growth plate than the other.The tethering effect of the osteochondroma on growth is directly related to the size of thegrowth plate it came from. The larger the growth plate the less effect theosteochondroma has on longitudinal growth because the force of growth in the remaininghealthy part of the growth plate is so great. The smaller the growth plate the greater is thetethering effect since the percent of the growth plate involved is so great. Good examplesof this are the fibula in the lower limb and the ulna in the upper limb. We shall discussthe ulna in a future article. In the lower leg where there are two adjacent bones (tibia andfibula), an osteochondroma tethering the growth of one bone and not the other will leadto a deformity since the two bones are attached together. Therefore if the fibula isgrowing slower than the tibia the leg will grow towards the fibula. This leads to a valgusdeformity (knock-kneed) of the upper tibia and a valgus deformity of the ankle (tiltedoutward). Osteochondromas between the tibia and fibula can also lead to deformity ofthe adjacent bone. For example an osteochondroma of the distal tibia can lead todeformity of the adjacent fibula near the ankle.Osteochondromas of the distal femur (lower end of femur near the knee), do not typicallylead to any deformity or length discrepancy on their own. They protrude into thesurrounding soft tissues and can lead to symptoms related to soft tissue impingement dueto their bulk. On occasion they do lead to deformity of the knee which is related to theChapter One 1 Section Two
  • 29. tethering of soft tissues and not to bony deformity. For example osteochondromasaround the knee can lead to locking and flexion deformity of the knee joint (the knee jointcatches in a certain position and will not straighten out).Osteochondromas of the upper femur sprout off the femoral neck. Depending on thedirection they come from they lead to different problems. Commonly they lead toasymmetric growth of the neck of the femur resulting in a valgus femoral neck (morevertical than usual). This is usually not a problem. Valgus of the neck of the femur isusually symmetric and therefore does not lead to a leg length discrepancy. When theosteochondroma is too near the hip joint or if it expands the capsule of the hip joint, thiscan result in a hip joint contracture or subluxation. The typical hip joint contracture isfixed flexion deformity of the hip from an anterior osteochondroma. Patients presentwalking leaning forward with hyperlordosis of the spine (sway back) as they try andcompensate for the leaning forward effect of the hip by arching their back. Subluxationof the hip occurs due to the effect of the osteochondroma pushing the hip out of jointcombined with the effect of the valgus of the femoral neck.Treatment of the Lower Limb Deformities.Valgus Knee Deformity (Knock knee deformity)This deformity is usually in the upper tibia. There is usually a large osteochondromainvolving the upper end of the fibula. The fibular osteochondroma often tethers orenvelops the peroneal nerve. This is a very important nerve that is responsible forcontrolling the muscles that pull the foot up and out. Injury to this nerve results in a dropfoot (inability to pull the foot up). Correction of the valgus deformity of the upper tibiarequires an osteotomy (bone cut) of the upper tibia. All osteotomies of the upper tibia tocorrect valgus stretch the peroneal nerve even in patients without HME. In patients withHME and a fibular exostosis the nerve is very tethered and stretched even before surgery.The nerve can actually be inside the bone if the osteochondroma envelops it. Thereforeto correct the deformity safely the nerve must first be found above the fibula anddecompressed around the neck of the fibula. The osteochondroma of the fibula should beresected. If the upper fibular growth plate is considered to be damaged beyond recoverythen a segment of the fibula should be removed so that the two ends of the fibula do notjoin together again to prevent re-tethering of the tibia. Only after all of this is performedcan an osteotomy of the tibia be carried out safely to correct the valgus deformity. Thevalgus deformity can either be corrected all at once or gradually. Correcting it all at onceis usually performed by taking out a wedge shaped piece of bone and then closing thewedge to straighten the tibia. This can be fixed in place with a metal plate or with anexternal fixator. Gradual correction is carried out by minimal incision technique to cut thebone. The correction is achieved by use of an external fixator. This is a device that fixesto the bone by means of screws or wires that attach to an external bar or set of rings.Adjustment of the external fixator slowly corrects the deformity. This opens a wedgeinstead of closes a wedge of bone. This has the advantage of adding length to the legwhich if the leg is short already is advantageous. This type of external fixator is alsoused for limb lengthening. Therefore if there is a LLD the angular correction can beperformed simultaneous with lengthening. Gradual correction is safer than acute (all atonce) correction for correction of the valgus deformity.Chapter One 2 Section Two
  • 30. Another way to address the valgus knee deformity without addressing limb lengthdiscrepancy is hemi-epiphyseal stapling of the growth plate. This is perhaps the mostminor procedure possible and involves insertion of one or two metal staples on the medialside (inside) of the growth plate of the upper tibia. The metal staple straddles the growthzone on the medial side preventing growth of the medial growth plate while permittinggrowth on the lateral side. This allows the tibia to slowly autocorrect its alignment. It isa very slow process and may require several years. Once the tibia is aligned the staplecan be removed permitting resumption of growth from the medial side. There is a smallrisk of damaging the medial growth plate which could lead to a varus bowing deformityof the tibia. Stapling can also be used in the distal tibia to correct the ankle deformity.Valgus deformity of the anklePatients complain of walking on the outer border of the foot. Viewed from behind thisposture of the foot is very apparent. This deformity is often well tolerated. The lower endof the tibia tilts outwards towards the fibula. The lower end of the fibula is the lateralmalleolus. It is important for stability of the ankle. Since the fibula grows less than thetibia the lateral malleolus is often underdeveloped leading to lateral shift of the talus(ankle bone). This can eventually lead to arthritis of the ankle. Lateral tilt of the anklejoint is compensated by the subtalar joint (joint under the ankle) by inversion of the foot(turning of the foot in). Since this is a longstanding process the subtalar joint becomesfixed in this position of compensation for the ankle joint. Therefore if one tries to fix theankle joint tilt completely the foot will end up tilted inwards and the patient will bestanding on the outer border of the foot. Therefore one either has to accept the valgusankle or correct it together with the subtalar joint fixed deformity. This is best done witha circular external fixator (Ilizarov device). This correction involves gradual correctionof a minimally invasive osteotomy of the lower tibia and fibula together with distraction(pulling apart) of the subtalar joint contracture.Flexion deformity of the kneeThis deformity is usually related to tethering or locking of the soft tissues around theknee by distal femoral or proximal tibial osteochondromas. The treatment involvesresection of the offending exostosis and lengthening of the hamstring tendons if needed.Flexion deformity of the hip/subluxation of the hip/valgus upper femurThis is treated by resecting the offending osteochondroma of the femoral neck. This hipcapsule has to be opened to access these. At the same time to reduce the hip subluxation(hip coming out of joint) a varus osteotomy of the upper femur should be done (bendingthe femur inwards towards the joint). The bone can be fixed either by an internal metalplate or an external fixator.Limb Length DiscrepancyLimb length discrepancy under 2cm is usually not noticeable and does not requiretreatment. LLD over 2cm is usually noticed by the individual affected leading to selfcompensation by walking on the ball of the foot (toe down) or by tilting the pelvis andcurving the spine (scoliosis). Untreated LLD can lead to lower back pain, and long legarthritis of the hip. These take many years to develop. Individuals who compensate forChapter One 3 Section Two
  • 31. LLD by walking on the ball of the foot often develop a tight Achilles tendon. The easiestway to treat LLD is by using a shoe lift. I generally prescribe a shoe lift one cm less thanthe LLD. Shoe lifts of up to 1cm can be easily accommodated inside a shoe. Greaterthan 1cm should be added to the outside of the shoe.Wearing a shoe lift prevents problems of the back, hip and ankle from developing. LLDcan also be equalized surgically. This can be done by either shortening the long leg orlengthening the short leg. In children shortening the long limb is achieved by surgicallyclosing the growth plate of the lower femur or the upper tibia prematurely(epiphysiodesis). This is a small minimally invasive procedure with few complications.The accuracy of this method depends on the ability of the surgeon to predict the LLD atmaturity and the rate of growth of the long limb. The accuracy of LLD equalization withthis method is ± 1cm. After growth of the skeleton has ceased (skeletal maturity)epiphysiodesis is no longer an option. Shortening in adults is carried out by removing asegment of the bone and fixing the bone in place with a metal rod that is inserted into themarrow cavity (locked intramedullary nail). In the femur this procedure can be donethrough very small incisions, and shortening up to 5cm (2 inches) can be safely achieved.In the tibia this procedure requires bigger incisions and has greater risk and is usuallylimited to 3cm (1.25 inches).Lower limb lengthening is the other way to correct LLD and can be carried out in bothchildren and adults and at almost any age. To lengthen a limb the bone is cut through avery small incision (1cm) and then the two ends of the bone are pulled apart at a gradualrate of 1mm/day (1/25 inch/day). Since bone is a living substance it grows new bone torepair the break. By pulling the bone apart at a gradual rate, we prevent the bone endsfrom joining together. Instead new bone if formed in the growing gap between the boneends. Once the desired lengthening is achieved the bone is held in place until it joinstogether. The new bone that was formed in the gap becomes stronger as calciumaccumulates in it. Eventually this new bone achieves the strength of normal bone. Thereare various devices that are used for limb lengthening. The majority of these are externalfixators. An external fixator is an external frame or brace that attaches directly to thebone by means of thin (1.8mm- 1/16”) tensioned wires or thicker (6mm- ¼”) screws(half-pins). The frame of the fixator is either shaped like a bar (monolateral fixator: e.gOrthofix, EBI, Wagner, monotube) or has rings and arches (circular fixator: Ilizarov,Taylor Spatial Frame, Sheffield). More recently these systems have become hybridizedand have elements of both monolateral and circular fixators. The circular fixators can beattached to the bone by means of wires that go from one side of the limb to the otherpassing through the skin on one side, then through the bone and then exiting the skin onthe other side. Wires have much smaller diameters than half-pins and achieve theirstrength by being tensioned across the ring, like tensioning a guitar string. Half pins areof much larger diameter and only pass through the skin on one side. They fix to the boneby means of a screw-like thread. To lengthen the limb the fixator has a screw mechanismwhich allows for small adjustments that pull the bone apart. The bone is pulled apartbecause the fixator which is attached to the bone above and below the break in the bone,lengthens as the screw mechanism is turned. The typical lengthening rate is 1/4mm, 4Chapter One 4 Section Two
  • 32. times a day, for a total of 1mm/day. There is even a motorized attachment which can beused for lengthening (Autogenesis). This lengthens at the same rate of 1mm/day dividedinto hundreds of small lengthenings. This may reduce the pain of lengthening. It is alsomore gentle on the soft tissues (nerves, muscles) that must stretch and grow as the bone ispulled apart.The most common complication with external fixator lengthening is superficial pininfection. This minor complication is to be expected. It is also easily treated by takingoral antibiotics at the first sign of infection (redness, tenderness, and drainage around apin site). Deeper infection of the soft tissues and bone is quite rare, but if it occursusually requires removal and possible replacement of the problem pin, IV antibiotics andsometimes surgery to debride (remove dead tissue) the soft tissue and bone. Othercomplications include tightness of muscles which can limit the range of motion of theadjacent joints or even pull the adjacent joints into a fixed position that interferes withfunction (e.g. equinus contracture of the ankle (fixed toe down position) is due totightness of the Achilles tendon that develops during lengthening). To prevent problemswith joints and muscles it is essential to do daily range of motion and stretching exerciseswith physical therapy, and to maintain that stretch by using foot or knee splints.Sometimes it is necessary to either immobilize a joint by extending the external fixationacross the joint to hold the joint in a functionally good position (e.g. foot fixation at 90°with tibial lengthening to prevent equinus). In some cases it may be necessary tosurgically lengthen some of the tendons or fascia to prevent or treat contractures (e.g.Achilles tendon lengthening). Bone complications can also occur. These include toorapid or too slow bone formation. Too rapid formation (premature consolidation) canprevent further lengthening and requires rebreaking the bone to continue lengthening. Toprevent this the lengthening rate may have to be increased. Poor bone formation can alsooccur (delayed consolidation). This requires more time in the external fixator until thebone is fully healed. Complete or partial failure of bone formation leads to a bone defectand may require a bone graft to get the bone to heal.There are two phases to the lengthening process. The first is the distraction phase whenthe bone is being pulled apart at one mm per day. The second is the consolidation phasewhen the bone is hardening while it is being held in place by the external fixator. Thefixator cannot be removed until the bone is completely healed. If the fixator is removedbefore that time the bone will bend, shorten and/or break. The best way to tell if the boneis fully healed is by x-ray. Even with x-rays it is not uncommon to misjudge the strengthof the bone and remove the fixator prematurely. In many cases we apply a cast for anadditional month of protection to minimize the risk of refracture. It is better to leave thefixator on an extra month than to take it off a day too early. Patients are often impatientat this stage and push their doctors to take the frame off. An experienced limblengthening surgeon turns a deaf ear to these frustrations and refuses to remove the frameuntil the x-rays suggest that the bone is strong enough that it will not break or bend uponremoval. Most of the complications of lengthening occur during the distraction phase orafter removal. Few complications other than pin infection arise during the consolidationphase.Chapter One 5 Section Two
  • 33. External fixator lengthening has been the standard for the past one hundred years of thehistory of limb lengthening. In the past decade internal lengthening devices haveemerged. These permit gradual lengthening by means of a fully implantable telescopicintramedullary rod (a metal rod that fits inside the marrow cavity of the bone). Whilethere are several of these devices in use worldwide, there is only one at present FDAapproved in the USA. This is called the Intramedullary Skeletal Kinetic Distractor(ISKD). It is manufactured by Orthofix, Inc. At present it is on a limited release withonly a small number of surgeons trained to use it and of those only two centers with alarge experience with its use (Baltimore and Orlando). This device can only be used inpatients who are skeletally mature and therefore is not applicable in growing children. Itis also limited in its ability to correct deformities. Nevertheless it eliminates all of theproblems related to the pins of the external fixator, especially pin site infections, scarsand pin site pain. It also reduces the muscle tethering from the pins and makes thephysical therapy easier. The ISKD does present some new problems not experiencedwith external fixator lengthening. There is less control of the lengthening rate andrhythm which can lead to contractures, nerve problems and bone healing problems. Inthe femur there is a higher rate of premature consolidation while in tibia there is a higherrate of delayed consolidation. Some patients experience severe pain at the onset oflengthening and require an epidural for several days until this pain goes away. All in allhowever we consider this a major advance. We have performed over 50 such surgerieswith good success. None have been for MHE.Deciding between lengthening and shortening is based on a few factors. Shortening isonly applicable for discrepancies less than 5cm. Shortening is a much smaller procedurewhile lengthening is a bigger procedure and longer treatment. Lengthening has a highercomplication rate. Shortening cannot correct deformity on the short leg. Lengthening cansimultaneously correct deformity and length discrepancy. Shortening will decrease thepatients height by the amount of shortening (max 5cm : 2 inches). Lengthening does notdecrease height. Therefore in someone with less than 5cm of LLD and no deformity whois not short or concerned about the height loss, epiphysiodesis or shortening are goodalternatives for equalization or LLD. Most cases do have associated deformities andtherefore our preference is to perform one operation to simultaneously correct the LLDand the deformity at the same time.Chapter One 6 Section Two
  • 34. Chapter One: Orthopedics Section Three Multiple Exostoses of the Forearm Contributor: Dror Paley, MD, Director, Rubin Institute forAdvanced Orthopedics, Co-Director, International Center for Limb Lengthening at Sinai Hospital of Baltimore
  • 35. Multiple Exostoses of the Forearm Dror Paley, MDIntroductionThe forearm consists of two bones (radius and ulna) and six joints (elbow: radio-capitalarand ulno-humeral; wrist: radio-carpal and ulno-triquetral; radio-ulnar: proximal anddistal). Unlike the relationship between the tibia and fibula in the lower extremity theradius and ulna move functionally relative to each other to produce the movement ofsupination and pronation . Relative to the elbow they move together (flexion andextension). Although most wrist motion and stability comes from the articulationbetween the radius and the carpus, the ulna provides support for the ulnar side andprevents excessive ulnar deviation of the hand. The relationship between the radius andthe ulna is therefore one of the most functional relationships between any two bones.Exostosis formation of either bone can easily interfere in the function of the elbow, wristor forearm rotation. Since osteochondromas form from the growth plates they are usuallyfound at the ends of the bones but migrate towards the shaft of the bone with growth.Ulnar Osteochondromas: osteochondromas most commonly form from the distalgrowth plate. Unlike those of the radius the ulnar exostoses are typically sessile (nostalk) while those of the radius are often pedunculated (on a stalk). The osteochondromasof the ulna often lead to delayed growth of the ulna relative to the radius. The radiusgradually gets longer than the ulna. The slower growing ulna tethers the growing radiusleading to increased tilt of the radius towards the ulna with increasing ulnar deviation ofthe wrist. Over time, the discrepant rate of growth leads to subluxation and thendislocation of the proximal end of the radius (radial head) from the elbow (radio-capitellar joint). Dislocation of the radial head from the joint causes the upper end of theradius to deform into valgus (bent position). Occasionally an osteochondroma candevelop from the ulna side of the proximal radio-ulnar joint. This can also contribute todislocation of the radial head by pushing the radial head laterally.Radial Osteochondromas: osteochondromas from the radius can be divided into thosethat protrude towards the ulna and those that don’t. The latter don’t impede supination-pronation motion, while the former do. The radius and ulna may develop ‘kissingexostoses’ that meet in the interosseous space.Distal radius deformity: the distal radius has a normal inclination towards the ulna of23º. In MHE the slower growing ulna may tether the distal radius on the ulnar sideleading to increased distal radial tilt. This increased tilt appears as ulnar deviation of thehand. With time the carpus will subluxe ulnarly and proximally.Proximal radius deformity: the ulnar tether also exerts a dislocating force on the radio-capitellar joint. As the radial head subluxes it comes to rest against the lateral condyle ofthe humerus. To adapt to this chronic position the radial neck may grow into valgus.With time, the radial head may completely dislocate and protrude posteriorly.Length discrepancy: The entire forearm is shorter than the other side. The shortening ispredominantly in the ulna. Some shortening is also present in the radius.Chapter One 1 Section Three
  • 36. Clinical signs and symptoms: Patients are limited in their forearm rotation range ofmotion. The wrist is usually ulnarly deviated. There may be a prominence or bump if theradial head is subluxed or dislocated. This may be tender to being bumped. Elbow flexionand extension is usually not affeceted. A flexion deformity of the elbow may be present.Treatment considerationsExostoses that are obviously impeding forearm rotation (e.g. kissing exostoses, areusually resected. It is important to do this via two separate incisions to avoid a crossunion between the radius and ulna. Lengthening and deformity correction can beperformed as the first stage in the absence of exostoses that limit motion, or as the secondstage if exostoses are resected first.Lengthening Reconstruction Surgery (LRS): LRS refers to distraction surgery usingexternal fixation to lengthen and correct deformities of the forearm. The problem inMHE ranges from simple to complex.Simple cases: In simple cases, the primary deformity is relative shortening of the ulna.The radial tilt is minimal and does not need to be addressed. There is nosubluxation/dislocation of the radial head. The problem is therefore just shortening of theulna. If this is left untreated the secondary deformities of the radius will develop. Thetreatment is to perform an isolated lengthening of the ulna. I prefer to do this with acircular external fixator even though the lengthening is linear. A circular fixator allowssimultaneous fixation of the radius to the ulna. Without fixation of the radius,lengthening of the ulna will transport the radial head distally. This occurs because of thetough interosseous membrane between the radius and the ulna. The osteotomy of the ulnais usually at its proximal end. This allows correction of any flexion deformity of the ulna(elbow) and leads to faster healing than if the osteotomy is made through the mid-diaphyseal (middle) section of the ulna.Complex cases: In more complex cases the surgical plan includes correction of the distalradial deformity and or radial head dislocation. A circular external fixator is used.Proximally both the radius and ulna are fixed. The ulnar osteotomy is made proximallyand the radial osteotomy is made distally. This type of frame simultaneously correctsshortening of the ulna and tilt of the distal radius. If the radial head is dislocated then thetreatment is staged. The first step is to lengthen the ulna with a pin connecting the radiusand ulna distally. This transports the radius distally and reduces the radial head. If theradial head does not reduce spontaneously then at a second stage surgery the radio-capitellar joint is opened and the radial head reduced at surgery and is held with an olivewire. If there is both distal radial tilt and dislocation of the radial head then the radialhead is reduced first and then at a second stage the wire pulling the radius and ulnadistally is removed and the distal radius osteotomized for deformity correction andlengthening.With staged surgeries many of the deformities of MHE of the forearm can be corrected.Combined with removal of the obstructing exostoses improved range of motion offorearm rotation is obtained.Does hemiepiphysiodesis stapling have a role in MHE? I have no experience with this inthe upper extremity. Theoretically, it should work for the distal radius. We areconsidering correction of the distal radial tilt by stapling in combination withoverlengthening of the ulna. Overlengthening of the ulna can help delay recurrence.Overlengthening of up to 2 cm is practical. Fixation of the hand is not required if thelengthening of the radius is less than 3 cm.Chapter One 2 Section Three
  • 37. Chapter Two: Genetics Section One The Genetics of Hereditary Multiple Exostosis (HME)Contributors: Sandra A. Darilek, MS, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Jacqueline T. Hecht, Ph.D., Department of Pediatrics, University of Texas-Houston Medical Center, Houston, TX
  • 38. The Genetics of Hereditary Multiple Exostosis (HME) Sandra A. Darilek, MS and Jacqueline T. Hecht, PhDIntroductionHereditary multiple exostosis (HME) is a skeletal disorder characterized by the presenceof numerous bony outgrowths (osteochondromas or exostoses) that develop next to thegrowth plates of all the long bones (Solomon 1963). The most striking clinical feature ofHME is the numerous cartilage-capped exostoses, which are associated with the entireskeleton. Skeletal surveys suggest that a solitary exostosis can be found in 1-2% of thegeneral population (Mirra 1989). A diagnosis of HME is made in individuals where thepresence of multiple exostoses has been noted on clinical and/or radiologic examination.The average age at identification of a first exostosis is three to four years with 96% ofindividuals with HME developing exostoses by the age of 12 (Schmale et al. 1994;Wicklund et al. 1995).In addition to having exostoses, individuals with HME can have other skeletal and non-skeletal complications. Skeletal complications include limb discrepancy and bonydeformities such as bowed radius, conical ulna, and valgus deformity of the hip and ankle(Solomon 1963; Karasick et al. 1997; Vanhoenacker et al. 2001). Mild short stature isalso a characteristic feature of the condition with the mean height being 170 ± 7.9 cm formales and 155 ± 6.9 cm for females (Wicklund et al. 1995). The presence of exostosescan lead to a number of non-skeletal complications such as compression of tendons,muscles, ligaments, blood vessels, and nerves, all of which can cause pain. Blood vesselinvolvement has been found in 11.3% of individuals with HME, while peripheral nervecompression and spinal cord compression have been found in 22.6% and 0.6% ofindividuals with HME, respectively (Wicklund et al. 1995). A recent study focusing onpain in HME found that 84% of individuals report having pain as a result of having HME(Darilek et al. 2004). By far the most severe complication of HME is the malignanttransformation of an exostosis into a chondrosarcoma. Recent studies estimate thelifetime risk of malignant degeneration to be about 2-4% for individuals with HME(Schmale et al. 1994; Wicklund et al. 1995; Darilek et al. 2004). Many individuals withHME undergo surgery as a result of having HME-related complications. Studies haveshown the 66-74% of individuals with HME undergo at least one operation for theirexostoses, with the average number of surgeries being two to three (Schmale et al. 1994;Wicklund et al. 1995).InheritanceHME is an autosomal dominant condition with a penetrance ranging from 96 to 100%(Schmale et al. 1994; Wicklund et al. 1995). Estimates of the prevalence of HME haveranged from 0.9 in 100,000 in a European population to 100 in 100,000 in a small, closedpopulation of the Chamorros of Guam (Voutsinas and Wynne-Davies 1983; Krooth andCunningham 1986; Hennekam 1991). A more recent study in the state of Washingtonfound the prevalence to be at least one in 50,000, however, this is thought to be anunderestimate as more mildly affected individuals do not come to medical attention(Schmale et al. 1994). Most people with HME have a family history of the condition.Solomon (1963) reported that 66% of individuals with HME have a family history whilemore recent studies have increased this estimate to 70-90% (Schmale et al. 1994;Wicklund et al. 1995).Chapter Two 1 Section One
  • 39. Gene LinkageLinkage studies were conducted to locate the gene or genes leading to HME. It was longsuspected that a gene for HME would map to the Langer-Giedion region on chromosome8. Langer-Giedion syndrome is a rare, autosomal dominant disorder in which individualshave multiple exostoses, characteristic facial features, and cone-shaped epiphyses and arefrequently mentally retarded (OMIM #150230). The exostoses found in HME andLanger-Giedion syndrome are indistinguishable. In addition, a patient with HME and abalanced chromosomal translocation involving chromosomes 8 and 11 had beendescribed, adding to the evidence for the presence of an HME gene on chromosome 8(Ogle et al. 1991). In order to determine if a gene for HME was indeed located onchromosome 8, Cook et al. in 1993 conducted linkage analysis on elevenmultigenerational families with HME. They found significant evidence for linkage of adisease locus to the Langer-Giedion region on chromosome 8 for 70% of the familiesstudied. This finding also indicated that HME is a genetically heterogeneous disorder,having at least one other locus somewhere else in the genome. In 1994, Wu et al. studiedtwo large, multigenerational families with HME, for which linkage to chromosome 8 wasexcluded, in order to try to localize other genetic loci for HME. They performed agenome-wide search and found evidence for a second locus for HME on chromosome 11.Linkage to a third locus on chromosome 19 was also reported by Le Merrer et al. in 1994.In 1996, the linkage to chromosomes 8 and 11 was confirmed by Blanton et al. and in2001 linkage analysis conducted by Francannet et al. confirmed that there are at leastthree EXT loci, with 69% of their families showing linkage to EXT1 on chromosome 8,21% to EXT2 on chromosome 11, and 3% to EXT3 on chromosome 19 (Blanton et al.1996; Francannet et al. 2001). These findings suggested that these three loci account forover 90% of cases of HME, but that at least one additional HME locus might exist.However, neither the EXT3 gene nor any additional EXT genes have been cloned andthese finding have not been confirmed in other studies.GenesOf the three genes linked to HME, two have been cloned: EXT1 on chromosome 8q23-q24 and EXT2 on chromosome 11p11-p12. Homologous genes have been found in mice,Caenorhabditis elegans, Drosophila, and Xenopus (Lin and Wells 1997), Stickens et al.1997, (Bellaiche et al. 1998; Katada et al. 2002)]. EXT1 and EXT2 are large genes.EXT1 is made up of eleven exons spanning over 250 kilobases while EXT2 containsfourteen exons and is spread over a region of more than 100 kilobases (Ludecke et al.1997). The genes code for ubiquitously expressed proteins of 746 (EXT1) and 718(EXT2) amino acids and share approximately 70% similarity at the amino acid level (Ahnet al. 1995; Wuyts et al. 1996). Both the EXT1 and EXT2 proteins have been found tolocalize predominately to the endoplasmic reticulum but function in the Golgi apparatusas hetero-oligomers to synthesize heparan sulfate chains (Lin and Wells 1997;McCormick et al. 1998; McCormick et al. 2000). Normally functioning EXT1 and EXT2proteins are required for proper bone growth. Since both proteins play a role in thedevelopment of benign bone tumors and there is an increased risk for individuals withHME to develop chondrosarcoma, it is thought that the EXT genes function as tumorsuppressors. This role has been supported by loss of heterozygosity (LOH) studies thathave revealed that both the EXT1 region on chromosome 8 and the EXT2 region onchromosome 11 show LOH in HME-related and isolated chondrosarcomas (Hecht et al.1995; Raskind et al. 1995; Hecht et al. 1997).Chapter Two 2 Section One
  • 40. MutationsResearch has shown that approximately 64-76% of families with HME have a mutationin the EXT1 gene and approximately 21-30% have a mutation in the EXT2 gene (Dobson-Stone et al. 2000; Wuyts and Van Hul 2000; Francannet et al. 2001). Currently, 66different mutations have been found in the EXT1 gene and 31 different mutations havebeen found in the EXT2 gene. The EXT1 mutations include thirteen nonsense mutations,twelve missense mutations, and four splice sites mutations as well as 37 mutations thatconsist of small insertions or deletions. The majority of the EXT1 mutations have beenfound to cause premature termination of the EXT1 protein. While most of the mutationsreported are private mutations, two mutations, 1469delT and C1018T, have been reportedin nine and ten unrelated patients, respectively (Wuyts and Van Hul 2000; Francannet etal. 2001). The distribution of the mutations over the EXT1 gene has been analyzed andreveals that while mutations occur throughout the entire length of the gene, most of themutations are distributed over the first six exons of the gene with the last five exons,which contain a conserved carboxyterminal region, having significantly fewer mutations(Wuyts and Van Hul 2000). The EXT2 gene has been shown to have a comparablespectrum of mutations. Eleven of the 31 reported mutations are nonsense mutationswhile four are missense mutations, three are splice site mutations, and thirteen areframeshift mutations (Wuyts and Van Hul 2000; Francannet et al. 2001). As in EXT1,most of the mutations are private mutations that are distributed over the first eight exonsof the gene, again leaving the carboxyterminal region with fewer mutations than onewould expect with a random distribution (Wuyts and Van Hul 2000). The majority of theEXT mutations are expected to cause premature termination of the EXT proteins leadingto loss of function of the proteins (Francannet et al. 2001). A multi-step model wasproposed to describe the development of an exostosis but there is little experimental datato support this model. Only heterozygous mutations have been identified in the vastmajority of exostosis samples with only a few exostosis samples demonstrating multiplemutations or LOH (Hall et al. 2002).Genotype-Phenotype Correlations In 2001, Francannet et al. conducted a clinical survey and mutation analysis for 42families with HME, consisting of 217 affected individuals, in order to determine whetherthere is any correlation between HME phenotype and genotype. They divided thefamilies into two groups based on the phenotypic expression of the disease. The firstgroup, referred to as group S, included families with severely affected members while thesecond group (group M) included families whose members had a moderate HMEphenotype. They also further divided group S into four subgroups labeling them as typeIS to IVS, with IVS being the most severely affected group overall. Of the 42 familiesstudied, seven belonged to group M and 35 to group S. Of the group S families, 10 werelabeled type IS, five type IIS, eight type IIIS, and two type IVS. Most of the familieswith a moderate phenotype (group M) were found to have EXT2 mutations, while all ofthe type IIS, IIIS, and IVS families except one were found to have EXT1 mutations. Themore severe HME phenotype (type S) was significantly associated with EXT1 mutationswhile a more moderate phenotype was associated with EXT2 mutations. Of note,chondrosarcomas were only found in patients with EXT1 mutations. The only correlationfound between phenotype and location of mutation in the EXT genes was found in theIVS group (most severe phenotype). Mutations associated with this group of patientswere consistently located in the first exon of EXT1. Phenotypic variability has also beennoted in HME. In this study, 2/3 of families with an EXT1 mutation were noted toChapter Two 3 Section One
  • 41. exhibit phenotypic variability, while in all but two families with EXT2 mutationsmembers showed a homogeneous phenotype (Francannet et al. 2001).This genotype-phenotype analysis suggests that more severe HME phenotypes presentingwith large number of exostoses, short stature, and/or vertebral exostoses are morecommonly found in individuals with an EXT1 mutation. One concern about the study isthe criteria used for categorizing phenotype severity. The researchers used five factors tojudge severity: age at onset (severe if less than or equal to 3 years), number of exostosesat time of evaluation (severe if greater than or equal to 10), location of exostoses (severeif vertebral exostoses noted), stature (severe if less than or equal to the tenth percentile),and functional rating (severe if the rating was “fair”). For an individual’s phenotype tobe labeled severe, three or more of these factors had to be rated severe. The authors donot explain why these specific cutoffs are determined. There currently is no consensus asto what constitutes a severe versus a moderate HME phenotype and thus severity ratingscan be extremely subjective. Of note, the genotype-phenotype correlations were based onfamily phenotype, not on individual phenotype, and a family’s phenotype was basedsolely on the degree of severity of the most affected members. As a result, a family witha number of mildly or moderately affected members could have been labeled as severe ifa few of the members are found to have severe phenotypes. This can lead to a bias, asonly those most severely affected family members are considered when makinggenotype-phenotype correlations. In addition, it is not clear whether the study populationis made up of individuals ascertained from a clinic population or from the generalpopulation of individuals with HME. If the study population is a clinic population, it ispossible that only more severely affected individuals and families were studied, againbiasing the study toward a more severe phenotype by not including those individuals andfamilies who never come to medical attention due to being mildly affected by HME. Inorder to determine whether genotype-phenotype correlations can be made in HME,additional studies should be carefully undertaken and consider disease severity byindividual.Genetic Counseling and Genetic TestingMost individuals with HME have a parent who also has the condition, however,approximately 10% of individuals with HME have the condition as a result of a de novomutation and are thus the first person in their family to be affected (Schmale et al. 1994).Individuals with HME have a 50% chance of having an affected child. Genetic testingfor HME is available on a clinical basis. Testing consists of sequence analysis of theentire coding regions of both the EXT1 and EXT2 genes. The mutation detection rate hasbeen found to be approximately 70%, as sequencing of the coding regions of the genesmay not identify all mutations (Philippe et al. 1997; Raskind et al. 1998). If a mutation isnot detected by sequence analysis, fluorescent in situ hybridization (FISH) analysis canbe used to detect deletions in the EXT1 and EXT2 genes. Prenatal diagnosis throughchorionic villus sampling (CVS) at 10-12 weeks gestation or amniocentesis at 16-18weeks gestation as well as preimplantation genetic diagnosis (PGD) is available forindividuals for whom genetic testing has identified a disease-causing mutation. Thoughgenetic testing is available for HME, the severity of the condition cannot be predictedbased on mutation type. In fact, the severity of the condition varies even within membersof the same family. Genetic counseling is indicated for individuals and families withHME to aid them in understanding information about HME and making decisions basedon this information.Chapter Two 4 Section One
  • 42. AcknowledgementsThis work was partially supported by a grant from Shriners Hospital for ChildrenReferencesAhn J, Ludecke HJ, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE (1995) Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat Genet 11:137-43Bellaiche Y, The I, Perrimon N (1998) Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394:85-8Blanton SH, Hogue D, Wagner M, Wells D, Young ID, Hecht JT (1996) Hereditary multiple exostoses: confirmation of linkage to chromosomes 8 and 11. Am J Med Genet 62:150-9Darilek S, Wicklund C, Novy D, Scott A, Gambello MG, Johnston D, Hecht JT (2004) Hereditary multiple exostosis (HME) and Pain. Submitted Pediatr Ortho,Dobson-Stone C, Cox RD, Lonie L, Southam L, Fraser M, Wise C, Bernier F, Hodgson S, Porter DE, Simpson AH, Monaco AP (2000) Comparison of fluorescent single-strand conformation polymorphism analysis and denaturing high-performance liquid chromatography for detection of EXT1 and EXT2 mutations in hereditary multiple exostoses. Eur J Hum Genet 8:24-32Francannet C, Cohen-Tanugi A, Le Merrer M, Munnich A, Bonaventure J, Legeai- Mallet L (2001) Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet 38:430-4Hall CR, Cole WG, Haynes R, Hecht JT (2002) Reevaluation of a genetic model for the development of exostosis in hereditary multiple exostosis. Am J Med Genet 112:1-5Hecht JT, Hogue D, Strong LC, Hansen MF, Blanton SH, Wagner M (1995) Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. Am J Hum Genet 56:1125-31Hecht JT, Hogue D, Wang Y, Blanton SH, Wagner M, Strong LC, Raskind W, Hansen MF, Wells D (1997) Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies. Am J Hum Genet 60:80-6Hennekam RC (1991) Hereditary multiple exostoses. J Med Genet 28:262-6Karasick D, Schweitzer ME, Eschelman DJ (1997) Symptomatic osteochondromas: imaging features. AJR Am J Roentgenol 168:1507-12Katada T, Oogami S, Shima N, Kinoshita T (2002) cDNA cloning and distribution of XEXT1, the Xenopus homologue of EXT1. Dev Genes Evol 212:248-50Krooth CS, Cunningham L (1986) The PRIMOe Principle: Physicians in product- line Marketing. Health Exec 2:40-43Lin X, Wells D (1997) Isolation of the mouse cDNA homologous to the human EXT1 gene responsible for Hereditary Multiple Exostoses. DNA Seq 7:199-202Ludecke HJ, Ahn J, Lin X, Hill A, Wagner MJ, Schomburg L, Horsthemke B, Wells DE (1997) Genomic organization and promoter structure of the human EXT1 gene. Genomics 40:351-4Chapter Two 5 Section One
  • 43. McCormick C, Duncan G, Goutsos KT, Tufaro F (2000) The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci U S A 97:668-73McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F (1998) The putative tumour suppressor EXT1 alters the expression of cell- surface heparan sulfate. Nat Genet 19:158-61Mirra J (1989) Benign cartilaginous exostoses: Osteochondroma and osteochondromatosis. In: Bone Tumors: Clinical Radiologic and Pathologic Correlations. Lea and Febiger, Philadelphia., pp 1626-59Ogle RF, Dalzell P, Turner G, Wass D, Yip MY (1991) Multiple exostoses in a patient with t(8;11)(q24.11;p15.5). J Med Genet. 12:881-3Philippe C, Porter DE, Emerton ME, Wells DE, Simpson AH, Monaco AP (1997) Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. Am J Hum Genet 61:520-8Raskind WH, Conrad EU, 3rd, Matsushita M, Wijsman EM, Wells DE, Chapman N, Sandell LJ, Wagner M, Houck J (1998) Evaluation of locus heterogeneity and EXT1 mutations in 34 families with hereditary multiple exostoses. Hum Mutat 11:231-9Raskind WH, Conrad EU, Chansky H, Matsushita M (1995) Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11. Am J Hum Genet 56:1132-9Schmale GA, Conrad EU, 3rd, Raskind WH (1994) The natural history of hereditary multiple exostoses. J Bone Joint Surg Am 76:986-92Solomon L (1963) Hereditary multiple exostosis. J Bone Jt Surg 45B:292-304Vanhoenacker FM, Van Hul W, Wuyts W, Willems PJ, De Schepper AM (2001) Hereditary multiple exostoses: from genetics to clinical syndrome and complications. Eur J Radiol 40:208-17Voutsinas S, Wynne-Davies R (1983) The infrequency of malignant disease in diaphyseal aclasis and neurofibromatosis. J Med Genet 20:345-9Wicklund CL, Pauli RM, Johnston D, Hecht JT (1995) Natural history study of hereditary multiple exostoses. Am J Med Genet 55:43-6Wuyts W, Van Hul W (2000) Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes. Hum Mutat 15:220-7Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul EV, De Boulle K, de Vries BB, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AM, McGaughran J, Halley DJ, Willems PJ (1996) Positional cloning of a gene involved in hereditary multiple exostoses. Hum Mol Genet 5:1547-57Chapter Two 6 Section One
  • 44. Chapter Two: Genetics Section Two The Genetics of Multiple Hereditary Exostoses – A Simplified ExplanationContributor: Wim Wuyts, Ph.D., Supervisor, DNA Diagnostics, Department of Medical Genetics, University and University Hospital of Antwerp, Belgium
  • 45. The Genetics of Multiple Hereditary Exostoses – A Simplified Explanation Wim Wuyts, Ph.D.Multiple Hereditary Exostoses - General aspectsIntroductionHereditary Exostoses (MHE), also often referred to as Hereditary Multiple Exostoses(HME), is a bone disorder that affects mainly the long bones. Recently the term MultipleOsteochondroma (MO) was suggested by the World Health Organization (WHO) as thepreferred term to refer to this disorder and throughout this article both abbreviationsMO/MHE will be used. MO/MHE is characterized by the presence of bonyprotuberances, which are described as osteochondromas or exostoses. They are locatedmainly near the joints and are often accompanied by skeletal deformities.MO/MHE was first described in the year 1786, while the name multiple exostoses wasfirst proposed in 1876. In the literature one can find many other names describing thisdisorder; such as diaphyseal aclasis, chondral osteoma, osteochondromata, multiplecartilaginous exostoses, (multiple) exostosis, deforming chondreodysplasia, osteogenicdisease, etc.Single osteochondromas or exostoses are very common in the general human population(1 to 2%) but the incidence of multiple osteochondroma is estimated to be 1 in 50,000.However, isolated communities have been described where a much larger fraction of thepopulation is affected. MO/MHE is not a unique human disease, as osteochondromashave been found in many species including cats, dogs, sheep, horses, lizards, lions, etc.A large osteochondroma was even found on the bones of a dinosaur.Clinical aspectsMO/MHE is a condition a person is born with and osteochondromas can be present atbirth but in most patients they are noticed within the first six years of life. By the age of12, almost all patients have been diagnosed. Most affected bones are the femur, tibia andfibula, but this is very variable from patient to patient. In theory every bone which isformed by endochondral bone formation (a process of bone formation in which cartilageis formed first, which then is replaced by bone) can be affected. Facial bones remainnormally unaffected. MO/MHE is characterized by great variation in number, size,location and shape of the osteochondromas, even within a family. The osteochondromascontinue to grow until closure of the growth plates at the end of puberty. Development ofnew osteochondromas or further growth at later age is not common but has beendescribed. In addition to the presence of the bony outgrowths, skeletal deformities suchas bowing and shortening of the forearm, knee, hip and ankle deformities can be present.Mild short stature is also observed in many patients.Chapter Two 1 Section Two
  • 46. Many complications have been observed in MO/MHE patients, including compression oftendons, nerves, muscles, ligaments and spinal cord. The pressure of theosteochondromas on neighboring tissues and organs causes often almost permanent pain.The most serious complication is the development of a malignant tumor (achondrosarcoma) out of an osteochondroma, mostly occurring at adult age. This event isobserved in 1 to 5% of the cases and is often preceded by abnormal growth of theosteochondroma or changes in the cartilage cap which covers the osteochondroma. Theonly known treatments for MO/MHE are surgical removal of the osteochondromas,(which often grow back at the original site) and surgical procedures to correct bonedeformities and limb length discrepancies. Surgery, physical therapy and painmanagement are currently the only options available to MO/MHE patients, and theirsuccess varies from patient to patient and many struggle with pain, fatigue and mobilityproblems throughout their lives. At present there is no definite cure for MO/MHE.In addition to MO/MHE, two syndromes have been described where multiple exostosesare one of the symptoms: the Langer-Giedion syndrome (LGS) and the Proximal 11pdeletion syndrome (P11pDS). Patients suffering from LGS have multipleosteochondromas, but also show typical characteristic features such as a bulbous nose,protruding ears, sparse hair, cone-shaped epiphyses and often mental retardation. Patientswith P11pDS syndrome (also called Potocki-Shaffer syndrome) have multipleosteochondromas, skull defects and often mental retardation.Genetic aspectsMO/MHE is an autosomal dominant hereditary disorder. This means that a patient withMO/MHE has a 50% chance of transmitting the disorder to his/her children, so he/she hasa 50% chance that his/her child will also have MO/MHE and 50% that this is not thecase. This is equal for both male and female patients. Normally the disorder does not skipa generation. So if one of the parents does have MO/MHE and the child does not, thischild will normally only have unaffected children. However, some patients have verymild symptoms so it may only look like they are unaffected. In this case, their childrenare still at 50% risk of developing MO/ MHE. This may create a situation where it seemsthat the disorder skips a generation. In such cases, genetic analysis may reveal the truestatus. In a large number of patients there is no previous family history of MO/MHE andboth parents are unaffected. In these patients a new mutation has occurred. Thesepatients have then again a 50% risk of transmitting the disorder to their children.To understand why MO/MHE is an autosomal dominant disorder one has to understandthe basic principles of heredity. All our genetic information, which determines a greatdeal of the development of our body, lies within our DNA. This DNA is organized inchromosomes, which are numbered from 1 to 22 while the sex determining chromosomesare named X and Y. At the moment of conception, the egg cell which comes from themother fuses with the sperm cell, which is provided by the father. The egg cell contains23 chromosomes (chromosome 1 to 22 and an X chromosome) and the sperm cellcontains 23 chromosomes (1 to 22 and an X or Y chromosome). After fertilization, afertilized egg with 46 chromosomes is formed from which an embryo and eventually ahuman being will develop. During this process the cells will divide with duplication ofChapter Two 2 Section Two
  • 47. the DNA. Therefore, in the human body (almost) every cell (with the exception of theegg and sperm cells) contains the 46 chromosomes containing the entire DNA content.Males have one X and one Y chromosome, females have two X chromosomes. Certainparts of our DNA, the so-called genes, contain all the information necessary to makeproteins. Every gene is located on a certain chromosome. If such gene contains an error,which is called a mutation, this can affect the formation and/ or function of this gene andthus the function of the corresponding protein. Loss of altered function of this protein canthen result in a visible defect or disorder.At present we know that there are two such genes, the EXT1 gene on chromosome 8 andthe EXT2 gene located on chromosome 11, which are important with respect toMO/MHE. If a mutation in one of these two genes occurs, this inactivates this geneand/or the corresponding EXT1 or EXT2 protein. Therefore, MO/MHE patients haveonly one functional EXT1 or EXT2 gene, so have only half of the functional EXT1 orEXT2 proteins compared to people without a mutation in EXT1 or EXT2. Both EXT1and EXT2 have a function in cartilage and bone development and it appears that theremaining EXT proteins are not enough for normal bone development. The fact thatMO/MHE patients still have one functional EXT gene (and EXT protein) is not enoughand therefore the effect of the mutation is dominant. This is in contrast with the so-calledrecessive diseases, such as, for example, cystic fibrosis (CF) where you only develop thedisease if you have a mutation in both genes. People with a mutation in only one of theirCF genes do not get CF but are only carriers of the disease. The chance for two parentswho are both carriers of having an affected child is in this case 25%.Approximately 60 to 70 % of MO/MHE patients have a mutation in the EXT1 gene and20 to 30% have an EXT2 mutation. In 10 to 20% of the patients, no mutation is found.This can be explained by the presence of a yet unknown, additional EXT-causing gene orby the fact that not all mutations can be detected by the techniques commonly used inDNA diagnostics for MO/MHE. The fact that most of the families have a differentmutation makes genetic analysis for MO/MHE very laborious and expensive, and it istherefore only performed in a few laboratories worldwide. At present, the outcome ofgenetic testing has no effect on determining orthopeadic care but genetic testing may givemore options in making choices in reproduction. Once the mutation is identified in onepatient, testing of family members is relatively easy and it can confirm their affected/non-affected status. Moreover, presymptomatic and prenatal diagnostics through chorionicvillus sampling (CVS) at 10-12 weeks gestation or amniocentesis at 16-18 weeksgestation is available and also preimplantation diagnostics (PGD) can be offered to thosefamilies for whom the disease-causing mutation has been identified.At present, it is still not very clear whether the differences in severity of the disease arerelated to whether the patient has an EXT1 or EXT2 mutation. There seems to be atendency that EXT1 mutations cause a more severe type of MO/MHE, but this needs tobe confirmed in larger studies. In addition, there is no explanation for the variation inseverity that is observed between patients within one family, thus with the samemutation. It is therefore at present impossible to make predictions with regard to severityof the condition based upon mutation type.Chapter Two 3 Section Two
  • 48. Concluding remarksAlthough still many questions remain unanswered, many aspects of MO/MHE have beenelucidated in the past years. The increasing understanding of the genetic and biologicalaspects of this disorder will increase the quality of the (genetic) counseling of MO/MHEpatients, which should always be offered when a diagnosis of MO/MHE is made.Selected literature1. Ahn J, Lüdecke H, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE: Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genet. 1995, 11:137-1432. Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK, Powell CM, Shaffer LG, Willems PJ: Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis and mental retardation, caused by deletions on the short arm of chromosome 11. Am J Hum Genet 1996, 58:734-7423. Francannet C, Cohen-Tanugi A, Le MM, Munnich A, Bonaventure J, Legeai-Mallet L: Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet 2001, 38:430-4344. Hennekam RCM: Hereditary multiple exostoses. J Med Genet 1991, 28:262-2665. Hunter J. The works of John Hunter, F.R.S. London: Longman, 1835.6. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K: The putative tumor suppressors EXT1 and EXT2 are glycosyltranserases required for the biosynthesis of heparan sulfate. J Biol Chem. 1998, 273:26265-262687. Luckert Wicklund C, Pauli RM, Johnston D, Hecht JT: Natural history study of hereditary multiple exostoses. Am J Med Genet 1995, 55:43-468. Lüdecke HJ, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ, Haan EA, Frydman M, Hamers GJH, Wells DE, Horsthemke B: Molecular dissection of a ontiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum Mol Genet 1995, 4:31-369. McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F: The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nature Genet. 1998, 19:158-16110. McCormick C, Duncan G, Goutsos KT, Tufaro F: The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the golgi apparatus and catalyzes the synthesis of heparan sulfate. PNAS 2000, 97:668-67311. Porter DE, Lonie L, Fraser M, Dobson-Stone C, Porter JR, Monaco AP, Simpson AH: Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint Surg Br 2004, 86:1041-612. Potocki L, Shaffer LG: Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2). Am J Med Genet 1996, 62:319-32513. Schmale GA, Conrad EU, Raskind WH: The natural history of hereditary multiple exostoses. 1994, 76:986-99214. Solomon L: Hereditary multiple exostosis. J Bone Joint Surg (Br) 1963, 45:292-304Chapter Two 4 Section Two
  • 49. 15. Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA: The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet 1996, 14:25-3216. Vanhoenacker FM, Van HW, Wuyts W, Willems PJ, De SA: Hereditary multiple exostoses: from genetics to clinical syndrome and complications. Eur J Radiol 2001, 40:208-21717. Virchow R: Ueber the Entstehung des Enchondroms und seine Beziehungen zur Enchondrosis und Exostosis cartilaginea. Monatsberichte der Koniglichen Preussischen Akademie der Wissenschaften 1876, 76018. Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul E, De Boulle K, de Vries BBA, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AMW, McGaughran J, Halley DJJ, Willems PJ: Positional cloning of a gene involved in hereditary multiple exostoses. Human Molecular Genetics 1996, 5:1547-155719. Wuyts W, Van Hul W: Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes. Hum Mut 2000, 15:220-22720. Wuyts W, Waeber G, Meinecke P, Schuler H, Goecke TO, Van Hul W, Bartsch O: Proximal 11p deletion syndrome (P11pDS): additional evaluation of the clinical and molecular aspects. Eur J Hum Genet 2004, 12:400-621. Zak B, Crawford BE, Esko JD: Hereditary multiple exostoses and heparan sulfate polymerization. Biochimica et Biophysica Acta 2002, 1573:346-355Chapter Two 5 Section Two
  • 50. Chapter Two 6 Section Two
  • 51. Chapter Two: Genetics Section Three Genetic Testing: Laboratories and Forms
  • 52. Universitair Universiteit Ziekenhuis Antwerpen Antwerpen CENTRUM MEDISCHE GENETICA EXT1 and EXT2 Gene testing at the Department of Medical Genetics, University of Antwerp (Belgium) Mutation analysis of the EXT1 and EXT2 genes will be performed by direct sequencing of all coding exons of both genes, including intron/exon boundaries. This results in the identification of a mutation in approximately 80% - 90% of the patients. Additional analysis to detect possible deletions involving the EXT1 or EXT2 gene will be performed by PCR analysis of intragenic EXT1 and EXT2 markers or FISH analysis (optional). Reporting of the results is expected within 2-4 months. Costs: Initial screening: 600 euro/sample for each gene analyzed. Normally both genes will be analyzed simultaneously. However, at request the analysis of only one gene or both genes stepwise is possible. If blood (heparin) is sent, FISH analysis is also performed. Confirmation: 300 euro/sample for screening for a known mutation. Detailed information of the exact position of the mutation should be provided. Inclusion of a control sample is preferred. Prenatal diagnosis: 600 euro/diagnosis. Prenatal diagnosis on chorion villi (CVS) must be announced in advance and can only be performed if adequate information is available. The lab should always be contacted before sending a CV sample. Maternal material (DNA or blood) is also required to test for possible maternal contamination (no additional cost). FISH: 300 euro/ sample Linkage analysis: If multiple members of a family are available linkage analysis can be performed to exclude/link one of the EXT genes. If this analysis is performed coupled with full mutation screening no additional cost will be charged and costs will thus be limited to 600 euro (index patient) and 300 euro for each additional family member that must be genotyped. It is possible to include individuals in the linkage analysis without genotyping them once the mutation has been identified. This should clearly be indicated at the request form. These individuals will not receive a result or invoice. An institutional invoice address for each sample should be provided or otherwise a check in euro made payable to Department of Medical Genetics University Hospital of Antwerp should be included when sending the sample. We do not send invoices directly to the patient.Universiteitsplein 1 2610 Antwerpen (BELGIE) Tel:+32(0)3 820 25 70 Fax:+32(0)3 820 25 66 : Prof. Markus NÖTHEN, MDConsultatie : Jenneke VAN DEN ENDE, MD, Marie-Noëlle VAN THIENEN, MD, Yolande VAN BEVER, MD, Bettina BLAUMEISER, MD, Martine BIERVLIET, MD, Winnie Courtens, MDCytogenetica : Bernadette VAN ROY, MSc, Jan WAUTERS, PhDDNA-onderzoek : Katrien STORM, MSc, Wim WUYTS, PhD, Guy VAN CAMP, PhD, Wim VAN HUL, PhD, Frank KOOY, PhD, Sven CICHON, PhD
  • 53. Sample:DNA analysis requires blood (20 ml – EDTA or heparin, but please include at least one tubeheparin) or DNA (50 µg). For FISH analysis we need 10 ml (HEPARIN).All samples should be sent toWim Wuyts, PhDDept. Medical GeneticsUniversity of AntwerpBuilding T (6th floor)Universiteitsplein 12610 WilrijkBelgiumSamples should be shipped at room temperature and should arrive in our lab preferable within48 hours. It is advised to contact the lab before sending any samples.Requests/ReportsAll requests for EXT mutation analysis should be sent by a genetic counselor or clinicianwith appropriate genetic knowledge with respect to multiple exostoses in order to ensureproper correspondence of the results to the patient. Reports will only be sent to the referringclinician or genetic counselor. No results will be mailed to the patient.Clinical informationClinical information is required. Please fill in attached clinical sheet for each patientFor additional questions, please contact Wim Wuyts.Wim Wuyts, PhDSupervisor DNA diagnosticsDept. Medical GeneticsUniversity of AntwerpBuilding T (6th floor)Universiteitsplein 12610 WilrijkBelgiumTel: 32-3-820.26.77Fax: 32-3-820.25.66Email:
  • 54. MULTIPLE OSTEOCHONDROMAS (MO) CLINICAL INFORMATION• Name patient:• Date of birth:• sex:•• Height : at age:• Age of onset of MO:• Number of osteochondromas at .......... (age) years (please circle) :1) 12) 2 to 53) 5 to 104) 10 to 205) >20• Site of osteochondroma (please tick):Site Site Sitedistal femur distal tibia footproximal femur proximal tibia kneedistal humerus distal fibula scapulaproximal humerus proximal fibula claviclepelvis spine other:............• Did the patient develop a chondrosarcoma? no yes at age: ......... location: .................................• Family history: 1) no family history 2) family history: please include pedigree
  • 55. MULTIPLE OSTEOCHONDROMAS (MO) CLINICAL INFORMATION (2)• Name patient:• skeletal deformities:1) no2) yes: please specify:Deformity Functional impairmentforearm decreased range of forearm rotationforearm with radial head dislocation decreased range of elbow flexionshortening of forearm decreased range of knee flexiongenu vaga other: .................................................other:................................• complications (vessel entrapment, tendon entrapment......):1) no2) yes: please specify: ........................................................................................................ ..........................................................................................................• additional comments/observations
  • 56. GeneDx, Inc. 207 Perry Parkway Gaithersburg, MD 20877 Phone (301) 519-2100 Fax (301) 519-2892 E-mail: EXT1 and EXT2 Gene Testing in Hereditary Multiple ExostosesAlso known as: multiple osteochondromatosis; hereditary multiple osteochondromata; multiplecartilaginous exostoses; diaphyseal aclasis; HMEMendelian Inheritance in Man Number: 133700Clinical features: Individuals with HME often develop benign cartilage-capped tumors (exostoses) at the ends of thelong bones or the surface of flat bones. Exostoses develop prior to skeletal maturity only. Bonydeformity, bowing of the long bones, limited range of motion, and premature osteoarthrosis may beassociated with hereditary multiple exostoses (HME). Exostoses also may cause complications byputting pressure on nearby tissues, nerves or blood vessels. A rare but severe risk in patients withmultiple exostoses is the development of malignant chondrosarcoma, which occurs in 1-2% of patientsInheritance pattern: There is genetic heterogeneity in HME, and at least two loci are known to be associated with thiscondition. GeneDx offers sequence analysis for both the EXT1 and EXT2 genes. A possible thirdgene thought to account for a small number of cases has not yet been identified. HME is an autosomaldominant trait, regardless of the gene involved. The risk to offspring of an affected individual is 50%.About 10% of individuals with HME have a negative family history, which may be due to a de novomutation or reduced penetrance of an EXT mutation in a parent. The literature suggests that diseasepenetrance is high [95%] and that most non-expressing carriers are female. According to a recentreview (Chansky and Raskind, 2000), 60-70% of identified mutations in HME are found in the EXT1gene, whereas 30-40% are in the EXT2 gene.Reasons for referral: 1. Confirmation of a clinical diagnosis 2. Genetic counseling 3. Prenatal diagnosis in at-risk pregnancies
  • 57. Test methods: Sequence analysis of the EXT1 and EXT2 genes are offered as separate tests. Using genomic DNA obtained from buccal (cheek) swabs or blood (5cc in EDTA), testing of EXT1 proceeds by bi- directional sequence analysis of all 11 coding exons. The EXT2 gene consists of 15 exons, and all coding exons (2-15) are sequenced in our analysis. Test sensitivity: In patients with HME, mutations are found in approximately 80% of individuals. Of those in whom mutations are identified, 70% of the mutations are found in the EXT1 gene and the remaining 30% in the EXT2 gene. Thus, the method used by GeneDx, Inc. to screen the EXT1 is expected to identify approximately 60% of mutations in HME. In individuals who are found to be negative on analysis of the EXT1 gene, screening of the EXT2 gene will identify the molecular basis of the disease in a further 25% of affected individuals. To date, there are no known distinguishing features within the clinical diagnosis of HME known to predict which gene is more likely to have a mutation. Multiple exostoses can be associated with contiguous deletion syndromes, which are not detected with our methods. Mutational spectrum: Most mutations in EXT and EXT2 cause premature truncation of the corresponding exostosen protein and are comprised of frameshift, splice site, and nonsense mutations. Missense mutations have also been seen. Costs and turn-around time: Mutation detection for EXT1 or EXT2 requires an affected individual and costs $1400 for each gene. We can test both genes concurrently if requested, however it is more cost-efficient to test them sequentially. DNA testing of relatives for a known mutation is $350. Pre-natal diagnosis using two samples (CVS, fresh amniocytes and/or cultured amniocytes) is $700. There may be additional cost for ruling out maternal contamination of the fetal sample, in some cases. For testing a new patient, turn-around time is approximately 6-8 weeks. For pre-natal diagnoses, where the mutation in the family is known, turn-around time is approximately 2 weeks. Fees are subject to change without notice. CPT codes for testing in either EXT1 or EXT 2 in Hereditary Multiple Exostoses 83891 x 15 units = $ 160 83898 x 15 units = $ 460 83894 x 15 units = $ 160 83904 x 15 units = $ 460 83892 x 4 units = $ 80 83912 x 4 units = $ 80 TOTAL = $ 1400 ICD9 Code for exostosis, unspecified site 726.91Chansky HA and Raskind WH (Updated [Aug 3, 2000]). Hereditary Multiple Exostoses. In: GeneReviews at GeneTests·GeneClinics:Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2002. Available at or
  • 58. GeneDx, Inc. 207 Perry Parkway Gaithersburg, MD 20877 Phone (301) 519-2100 Fax (301) 519-2892 E-mail: www.genedx.comCOLLECTION AND SHIPMENT OF BLOOD FOR GENETIC TESTING 1. Draw 5cc whole blood into a lavender top tube (containing EDTA). Label the tube with the patient’s name and your institutional identification number. 2. Wrap the tube in bubble wrap or other protective material and place inside a sealed plastic bag. 3. Place bag containing blood sample in a Styrofoam shipping box with a cool pack. DO NOT FREEZE THE BLOOD SAMPLE 4. Place the completed sample submission form, signed consent document, and payment option form, as well as any other paperwork in another sealed plastic bag or envelope. 5. Ship the sample by an overnight or second-day carrier, to arrive at GeneDx on a weekday (Mon through Friday).Ship to the following address:GeneDx, Inc.Accessions207 Perry ParkwayGaithersburg, MD 20877If you have any questions, please call GeneDx, Inc. at 301-519-2100, ore-mail genedx@genedx.comNOTE: DNA can also be shipped to GeneDx for use in our genetic tests, and this is oftenthe best choice for international samples. DNA can be shipped frozen, refrigerated, or atroom temperature. Ship to the same address as above. If available, please provideinformation about the concentration of DNA in the sample.
  • 59. GeneDx, Inc. 207 Perry Parkway Gaithersburg, MD 20877 Phone 301-519-2100 Fax 301-519-2892 E-mail: Web site: HOW TO COLLECT BUCCAL CELLSDNA can be prepared using cells obtained by swabbing the buccal mucosa (inside of the cheek). It is asimple non-invasive procedure and requires no exposure to blood or blood products.We have enclosed most of what you will need to obtain buccal cells. The onlyother thing you will need is a strong pair of scissors.PROCEDURE:1. Remove a Cytobrush Plus Cell Collector from the envelope touching only the“stick” end.2. Don’t rinse mouth before starting! Have the individual open his/her mouth.Twirl the brush on the inner cheek for 30 seconds. Be gentle but strong. DON’TSCRAPE SO HARD THAT THE CHEEK BLEEDS!3. Place the brush end of the Cytobrush Plus Cell Collector in the tube. Cut the“stick” with a pair of scissors (it takes a little effort!) at the level of the top of thetube. Replace the cap on the tube and close completely. 3a. Tubes are either (1) pre-labeled or (2) unlabeled. If labeled, be sure to place the correct brush in the correct tube. If unlabeled, you will have been sent small white labels on which to write the individual’s name and your institutional ID. Apply one label to each tube. You will need to prepare two labels for each individual.4. Repeat the process with another brush, this time brushing the inside of theother cheek.5. Mail the tubes with the brushes inside back to us in the enclosed envelope thatis addressed to GeneDx, Inc. They can be sent by regular mail.If you have any questions, please call GeneDx, Inc. at 301-519-2100, or
  • 60. GeneDx, Inc. 207 Perry Parkway Gaithersburg, MD 20877 Phone (301) 519-2100 Fax (301) 519-2892 E-mail: www.genedx.comDate Sample Obtained _____/_____/_____ mm/dd/yySample Type [ ] buccal brushes (must be GeneDx kits) [ ] blood in EDTA (lavender to – 5 mL for adults, 3 mL for children) [ ] skin punch biopsy, size ________mm [ ] DNA [concentration: __________µg/mL] [ ] fetal tissue: Specify type ___________________________________Patient Name ______________________________, _________________________, __________ Last name First name MIYour Patient Identifiers ___________________________________________________________Date of Birth _____/_____/____ mm/dd/yy History: Please provide any applicable information • Clinical diagnosis or family history, including anyGender [ ]Male [ ]Female [ ]Unknown reason to be considered for preferential priority (scheduled surgery, pregnancy management, etc.).Patient Address _______________________________ _______ Number and Street Apt ________________________ _____ _______________ City ST ZipcodePatient Phone Home ( ) ______ - _________ • Explain relationship to any other relatives submitted. Work ( ) ______ - _________ ext______ • Gestational age if pregnancy:TESTS REQUESTED: Mark on PAGE 2 of this form • ICD9 codes, if insurance submission is requested:REPORTING ADDRESS ADDRESS FOR DUPLICATE REPORTPhysician/CGC_____________________________________ ________________________________________Address ____________________________________ ________________________________________ ____________________________________ ________________________________________ ____________________________________ ________________________________________Phone ( ) ________-_________________ ( ) _________-_________________Fax *Important ( ) ________-_________________ ( ) _________-_________________Beeper ( ) ________-_________________ ( ) _________-_________________Email _________________@ ________________ __________________@ ________________PAYMENT: Submit the PAYMENT OPTIONS form Sample Submission Form and Test List Page 1 of 2 © GeneDx 07/04
  • 61. Periodic Fever Syndromes Hereditary Rickets____ Familial Mediterranean Fever (MEFV) ____ X-linked dominant hypophosphataemia (PHEX)____ Familial Hibernian Fever / TRAPS (TNFRSF1A) ____ Autosomal dom. hypophosphataemia (FGF23)____ Hyper- IgD Syndrome (MVK) ____ Autosomal rec. Vit. D dependent rickets (CYP27B1)____ Muckle-Wells /Familial Cold Urticaria/ NOMID (CIAS1) Alagille Syndrome (JAG1)Ectodermal Dysplasia syndromes ____ Tier 1 ____ Tier 2 if Tier 1 is negative____ X-linked hypohidrotic ED (EDA1 aka ED1, EDA)____ Autosomal rec/dom hypohidrotic ED (EDAR) Coffin-Lowry syndrome (RSK2)____ Clouston syndrome (GJB6, connexin30) _____Tier 1 ____Tier 2 if Tier 1 is negative____ Ectrodactyly-ED-Clefting (TP63, p63)____ Hay-Wells (TP63, p63) Hermansky-Pudlak Syndrome (HPS1 and/or HPS3) ____ HPS1 and HPS3 Puerto Rican mutationsCongenital Ichthyoses ____ HPS3 Ashkenazi splice mutation____ Lamellar ichthyosis (TGM1)____ Sjögren-Larsson syndrome (FALDH) Hereditary multiple exostoses (EXT1 and EXT2)____ Epidermolytic hyperkeratosis (KRT1, KRT10) _____ EXT1 only____ Ichthyosis bullosa of Siemens (KRT2e) _____ EXT2 if EXT1 is negative____ Vohwinkel syndrome (GJB2; connexin26) _____ Both EXT1 and EXT2____ Erythrokeratoderma variabilis (GJB3, connexin31; GJB4, connexin30.3) Noonan Syndrome (PTPN11)Other Keratin Disorders _____ Exons 3 and 8 onlyPachyonychia congenita _____ Remainder of gene (if 3 and 8 negative) ____ KRT16, KRT6a (PC1) _____ Entire PTPN11 gene ____ KRT17, KRT6b (PC2)____ Epidermolytic PPK of Vörner (KRT9) Other Disorders____ Unna-Thost disease (KRT1, KRT16) ____ Alexander Disease (GFAP)____ White sponge nevus (KRT4, KRT13) ____ Androgen Insensitivity Syndrome (AR)____ Steatocystoma multiplex (KRT17)____ Epidermolysis Bullosa Simplex (KRT5, KRT14) ____ Cartilage-Hair Hypoplasia (RMRP) ____ Dent Disease/ X-linked rec nephrolithiasis (CLCN5)Immune Deficiency Disorders ____ Dopa-Responsive Dystonia (GCH1)Chronic Granulomatous Disease ____ Fabry Disease (GLA) ____ X-linked (CYBB) and common recessive (NCF1) ____ Other autosomal recessive (NCF2, CYBA) ____ Hereditary angioedema (C1NH)Severe Combined Immunodeficiency (autosomal recessive) ____ Hirschsprung Disease (RET) ____incl. Omenn Syndrome (RAG1 and RAG2) ____ Holt-Oram (TBX5) ____Jak3 Deficiency (JAK3)____ X-linked agammaglobulinemia (BTK) ____ Holoprosencephaly (SHH, ZIC2, SIX3, TGIF)____ Leukocyte Adhesion Deficiency (ITGB2) ____ LEOPARD Syndrome (PTPN11, exons 7 and 12) ____ Mucolipidosis Type IV (MCOLN1)Bone Marrow Failure Syndromes ____ Nemaline myopathy (ACTA1)____ Fanconi Anemia (FANCA) cDNA sequence analysis____ Congenital amegakaryocytic thrombocytopenia (MPL) ____ Popliteal Pterygium Syndrome (IRF6)____ Shwachman-Diamond Syndrome (SBDS) ____ Pseudoachondroplasia/Mult Epiphyseal Dys (COMP)____ Congenital and cyclic neutropenia (ELA2) ____ VanderWoude Syndrome (IRF6)____ Dyskeratosis Congenita, X-linked (DKC1)____ Dyskeratosis Congenita, Autosomal (hTR) ____ X-linked Hydrocephalus (L1CAM)____ Diamond-Blackfan anemia (RPS19) ____ X-linked Retinoschisis (XLRS1) ____ XY Female Gonadal Dysgenesis (SRY sequencing)Cancer-Associated Syndromes____ Gorlin syndrome (PTCH)____ Cowden syndrome (PTEN) Alternatively, the following special services are____ Bannayan-Riley-Ruvalcaba syndrome (PTEN)____ Multiple endocrine neoplasia type 1 (MEN1,Menin) available for families with specific previously____ Multiple endocrine nepoplasia type 2A/ identified mutations. Check one per specimen. Familial Medullary Thyroid Carcinoma (RET)____ Multiple endocrine neoplasia 2B (RET) ___ Confirmation of mutation identified elsewhereHyperparathyroidism-Jaw Tumor Syndrome/ Parathyroid ___ Carrier Detection in relativescarcinoma/Familial Isolated Hyperparathyroidism (HRPT2) ___ Prenatal Diagnosis ____ Tier 1 ___ Tier 2 ____Entire geneFamilial Cutaneous Malignant Melanoma Required Info: Gene Name ________________ ____CDKN2A/ p16 ____ CDK4 ____ Both____ Peutz-Jeghers syndrome (STK11) Mutation(s) ____________________ Carney Complex (PRKAR1A) Relative’s Name or GeneDx Acc. No., if applicable:Developmental Eye Disease_____ Aniridia, other diagnoses (PAX6) ___________________________________ Anophthalmia, microphthalmia (SOX2)_____ Anophthalmia, microphthalmia (SIX6) Sample Submission Form and Test List Page 2 of 2 © GeneDx 07/04
  • 62. GeneDx, Inc. 207 Perry Parkway Gaithersburg, MD 20877 Phone 301-519-2100 Fax 301-519-2892 E-mail: Web site: Payment by credit card: The full amount of the test fee is charged at the time of sample submission. Name as it appears on card __________________________ Billing address __________________________ Mastercard Visa Discover __________________________ City, State Zip code American ExpressAccount Number |___|___|___|___| |___|___|___|___| |___|___|___|___| |___|___|___|___|Expiration date: Month _____/ Year _____ Please bill my credit card in the amount of $__________ for diagnostic laboratory tests performed by GeneDx, Inc. _______________________________ (Required) SignaturePayment by check or money order: Minimum of 75% of the cost of the test is required at the time ofsample submission*, with the remainder of the fee billed at the time of test completion. Check or money order enclosed in the amount of $________*For patients from outside the United States, 100% of the fee is due at the time of sample submissionInstitutional Billing: The hospital laboratory or referring physician can be billed. Please attach aletter stating the name of the contact person, address to which bill should be submitted, phone # andfax #, and information required on the invoice (e.g. CPT codes, HCFA1500 form). Call 301-519-2100with questions.GeneDx does not bill insurance companies directly unless a letter of agreement from the insurancecompany is included. This letter must address the cost of the specific test requested, and a statementdetailing the reimbursement rate, the name of the department or individual to whom the bill shouldbe sent (including address, phone number and fax number) and the patient’s name and policynumber. PLEASE BE AWARE THAT THE PATIENT IS RESPONSIBLE IN ALL CASES FORALL FEES NOT COVERED BY INSURANCE. ****** We also require a copy of BOTH SIDES of the insurance card ******Note: If you plan to apply to your insurance carrier for reimbursement of your expenses for this test,the following information may be helpful if GeneDx is requested by the carrier to prepare supportingdocumentation for you to use in your insurance claim:Insurance carrier __________________ Is this a Blue Cross/Blue Shield Plan? __YES __NOSubscriber Name __________________ Subscriber DOB ___/___/___ ID# ________________
  • 63. Chapter Three: Living with MHE Section One The Emotional Implications of Chronic Illness on MHE Patients and Their FamiliesContributors: Ronni Michelson, MSW, LSW; Susan Wynn, The MHE Coalition; Cathy Lloyd Reprinted from The MHE Coalition Newsletter No. 5, March 1, 2001
  • 64. The Emotional Implications of Chronic Illness On MHE Patients and Their Families Ronni Michelson, MSW, LSW and Susan WynnDisclaimer: This article is in no way a substitute for professional diagnosis andtreatment, but rather an overview of a subject which may be impacting some of ourreaders. As stated in the article, please seek out a mental health professional and/ormedical doctor with any questions or concerns.As sisters who have gone through numerous life crises together, we have seen the effectsof illness, both acute and chronic, on family dynamics. During the last few years,Multiple Hereditary Exostoses has become an integral part of our lives, and we wouldlike to share some of our observations and thoughts on the matter. MHE affects morethan the bones. It can also impact the emotional well being of the person who has it, aswell as the patients family.As we all know, no one passes through lifes journey unscathed, and for the most part wemanage to cope with the stress and/or anxiety as situations present themselves. However,chronic illness and pain present their own problems, and MHE itself carries with itadditional challenges.As MHE is a rare, orphan disease, many in the health care professions are just beginningto learn about the specifics of this disorder. Some families have reported experienceswhere doctors were unable to successfully diagnose and/or treat some of the ancillarycomponents of this disorder (i.e., fatigue, poor sleep habits, chronic and/or unexplainedpain, etc.). As the parent of a child with MHE, and from my experience in talking withother families, it appears that a holistic approach taken to care for the whole individual isundermined by treatment being fragmented. This is because the patient may be seen bymany specialists looking at symptoms from very different perspectives, and a correlationis not always made. This can be frustrating for many patients and families, since it tendsto invalidate the very real symptoms that are being experienced.Multiple members of a household may have the disease and depending on which memberrequires medical attention, is having pain, or requires surgery, family dynamics may be ina constant state of flux. A parent may be the caregiver one day, and a patient the next.Emotional responses to the disease are diverse and will vary depending upon attitude,growth and development, background and lifestyle. The capacity and willingness tounderstand the impact of the disease not only on the patient but also on each member ofthe family is vital to helping the family function as a unit.A lifetime challenged by pain, fatigue, surgery, and even restrictions on ones lifestylecan be devastating and may result in depression. It is important to understand that eachfamily member responds to this illness in different ways. There is no one way to respondor feel in handling stress (for example, the husband who has difficulty discussing thedisease, the mom who cries often, the sibling who behaves in an angry manner, the childwho feels guilty for "causing" these problems). While family members may not see eyeto eye at any one time, they need to persevere with respect for each other, allowing foropen and supportive communication.Chapter Three 1 Section One
  • 65. There are many coping mechanisms that can be utilized to deal with increased stresslevels. Often a combination of techniques will be the most effective approach. Thefollowing are just a few suggestions: Faith and spirituality Support Groups Drawing, journaling, and other expressive endeavors Relaxation techniques, such as guided imagery, deep breathing, meditation, aromatherapy Humor! If youve lost your smile, try to find it again. Laughter may not be the best medicine, but it certainly is good medicine! Adopt a healthy lifestyle, including mild exercise (remember to check with your physician before starting any new exercise program) and proper diet. Try to cut back on unhealthy habits (alcohol, caffeine, smoking, and a sedentary life style can actually stress the body and lead to increased, rather than decreased, tension). Restructure your priorities and add some pleasurable events into your day or week. While getting out to see a movie, or relaxing with a good book wont solve your problems, taking some time for yourself may just help you handle them a little better. If necessary, seek professional help. There are many options that your health care provider can discuss with you to help manage acute stress, anxiety, and/or depression.There are times when the impact of MHE gets to the point where medical intervention iswarranted, and where self-help measures are not enough, While that determination can bedifficult, there are some common signs to look for in adults, children, and adolescents: Persistent sad, "empty", or anxious mood Feelings of hopelessness, pessimism Feelings of guilt, worthlessness, helplessness Loss of interest or pleasure in ordinary activities Decreased energy, fatigue Difficulty in concentrating, remembering, and making decisionsChapter Three 2 Section One
  • 66. Sleep disorders including insomnia, oversleeping, or early morning awakening Irritability or restlessness Recurring thoughts of death or suicide Persistent physical symptoms that dont respond to treatment, including headaches, digestive disorders, and chronic pain.In addition, children and adolescents may experience some of these symptoms: Frequent vague, non-specific physical complaints such as headache, muscle aches, stomach aches or tiredness Frequent absences from or poor performance in school Talk of or efforts to run away from home Outbursts of shouting, complaining, unexplained irritability, or crying; increased anger or hostility Lack of interest in playing with friends, social isolation, poor communication; difficulty with relationships Extreme sensitivity to rejection or failureIf there is any doubt or questions, please seek medical/professional help. There are manytreatments available today to effectively deal with major depressive and/or anxietydisorders.Note: Some of the symptoms of MHE, such as fatigue, chronic pain, sleep disorders,etc. mimic or can be identical to those of major depression. Therefore it is even moreimportant to seek out professional help and try to find physicians familiar with MHEand to educate and provide information to mental health professionals, so that theetiology or origin of the problem is correctly diagnosed. Lifestyle modifications may beneeded to manage chronic symptoms such as chronic fatigue, in order to maximizepotential and limit unreasonable expectations that may in fact lead to a depressiveepisode.Chapter Three 3 Section One
  • 67. Resources to Learn More about Depression and Chronic IllnessCathy LloydTo find out more information on depression and chronic illness, check out some of thesesites. A number of them detail what depression is, and how it makes those suffering fromit feel. Many also have links to other helpful This is the web site for the National Mental Health Association.Contains information on depression, treatment and referrals to local screening Discusses how to cope with depression, depression in teens, anddepression among people with chronic A good site with stories centered around five friends who areall dealing with depression caused by different Has information and many links to other web sites and A U.K. organization, this site has many interesting Contains information and many links about depression and chronicillnessIf you dont have Internet access…The National Mental Health Association also has a phone number where you can get thesame information that is on their web site: 1-800-969-NMHA.The Youth Crisis Hotline: 1-800-448-4663. This is a 24-hour hotline with counselorsanswering the phone for teenagers to talk to about whatever situation they might bedealing with. The counselors listen and then refer the teen to someone local so they canget more help.Chapter Three 4 Section One
  • 68. Chapter Three: Living with MHE Section TwoPhysical Therapy for Patients with Multiple Hereditary Exostoses Contributor: Elena McKeogh Spearing, MA, PT, DPT, PCS, Physical Therapy Manager, Children’s Hospital of Philadelphia
  • 69. Physical Therapy for Patients with Multiple Hereditary Exostoses Elena McKeogh Spearing, MA, PT, DPT, PCSINTRODUCTION:What is Physical Therapy?Physical therapy is a profession that specializes in the diagnosis and management ofmovement dysfunction with the goal of restoring, enhancing, maintaining and promotingnot only optimal physical function but optimal wellness, fitness and quality of life as itrelates to movement and health. (1)Physical Therapy can only be performed by a licensed Physical Therapist. PhysicalTherapists possess specialized training at the post-graduate level and have a license topractice Physical Therapy. Many people who have suffered an injury, disease ordisability can benefit from Physical Therapy intervention. People who want to preventillness and disability can benefit from Physical Therapy as well. (1)What does a Physical Therapist do?A Physical Therapist performs an examination of many systems in the body. These arethe cardiovascular system, the neuromuscular system, the musculoskeletal and theintegumentary system. The physical therapist looks specifically at how much a joint canmove (range of motion) and how strong the muscles of the body are, including the heart.They look at what activities are hindered by pain or loss of motion or strength. PhysicalTherapists also examine balance, coordination and walking abilities.After a complete assessment of the information and an interview with the patient, thePhysical Therapist develops a plan of care to address any issues that are present. Basedon a patient’s personal goals, the Physical Therapist will develop a plan of care withspecific interventions to help the patient to achieve those goals. Physical Therapists striveto provide patient and family centered care, which recognizes the importance of thepatient and their family in the decision making process.Physical Therapy interventions can include stretching, strengthening, postural andaerobic exercises, functional activities and activities of daily living training. PhysicalTherapists also educate patients on the importance of wellness and injury prevention.Physical Therapists work as a team with other health care professionals includingphysicians, nurses, social workers, occupational therapists, speech therapists, recreationaltherapists, psychologists, and nutritionists.PHYSICAL THERAPY FOR PATIENTS WITH MHEHow can Physical Therapy help patients with MHE?For patients with Multiple Hereditary Exostoses, Physical Therapy is very important.The physical therapist works together with the orthopedic surgeon to determine the bestcourse of treatment for exostoses.Chapter Three 1 Section Two
  • 70. Pre-surgery:As described throughout this book, exostoses can be present in any bone of the body.Depending on the location and amount of pain and disability, the orthopedic surgeon mayor may not recommend surgery. Prior to surgery, the focus of Physical Therapy is toprevent or slow the loss of range of motion and function that can be caused by exostoses.Conservative treatment of exostoses may include physical modalities for pain relief.Although there is no evidence that exostoses growth can be prevented or slowed withPhysical Therapy, the disability associated with the exostoses can sometimes be managedeffectively with therapeutic interventions. Flexibility and strengthening exercises havebeen shown to decrease progressive disability in patients with other musculoskeletaldisorders like fibromyalgia and rheumatoid arthritis (1, 2, 3).Another focus of physical therapy, before and after surgery is required, may be toaccommodate some of the deformities that occur as a result of the exostoses. These couldinclude shoe lifts to make lengths of the legs equal, splints to protect joints and cushionsto make certain positions more comfortable. Equipment can also be provided to makeactivities of daily living easier and less painful. These include long handled utensils,brushes, reachers and grippers. Problems with mobility can be addressed with walkingaides like canes and crutches.Additionally, it has been shown that cardiovascular exercise can decrease pain andimprove overall well being in patients with musculoskeletal impairments (4, 5, 6, 7).A supervised exercise program that includes aerobic exercise and strength training mayalso help to decrease the pain and stiffness associated with MHE. While there are manybenefits to exercise, anything that causes increased pain in the area of exostoses shouldbe discontinued and reported to the medical professional.When the decision to have surgery is made, the patient’s individual needs after surgeryshould be anticipated. Often, patients can be seen for a pre-operative Physical Therapyvisit. During this visit, patients can learn how to use some of the equipment that they mayneed to use after the surgery. Practicing these new skills, like walking with crutches, ormoving around with a cast or fixator, can make the patient less apprehensive about therehabilitation process that will take place after the surgery.This pre-surgery visit is also beneficial to problem solving obstacles to post-surgeryrehabilitation. For example, many patients with painful exostoses under their arms, maynot be able to use traditional axillary crutches to maintain decreased weight bearing ontheir legs after surgery. In this case, forearm crutches or a walker may be moreappropriate for the patient. Additionally, a patient who does not demonstrate sufficientendurance may need a wheelchair to use for going outside of the house after surgery.Similarly, the patient who may have decreased weight-bearing abilities after surgery willneed to practice new approaches to everyday activities. These might include going up anddown stairs, getting into and out of a car, using the toilet, bathing and going to school orwork. The patient and the therapist can simulate these activities and problem solvetogether, before the surgery, so that they are prepared with successful strategies after thesurgery is performed.Chapter Three 2 Section Two
  • 71. Post-surgery:If it is determined that surgery is indicated to remove painful exostoses and increase apatient’s function, physical therapy is important following surgery. Depending on thesurgery, there may be a period of rehabilitation and the potential for a temporary decreasein function due to pain and muscle weakness. The focus of Physical Therapy aftersurgery is to minimize the pain and maximize the patient’s movement potential aroundthe area that the exostoses were removed.Some patients with MHE may only require a brief hospital stay after removal ofexostoses; others may require a rehab stay where more frequent and intense therapy isrequired. This depends on the location of the surgery, the extent of the surgery, theamount of function that is lost by the exostoses and the patient’s prior level offunctioning. During rehabilitation, therapy occurs daily and includes specificallystretching and strengthening of the muscles around the area of surgery. If pain andfunction were limited prior to the surgery, there may be some soft tissue limitations thatare present after the surgery that will require special attention.Based on the evaluation and orthopedic recommendations, weight bearing will bemonitored and progressed as directed. In procedures, which include limb lengthening,physical therapy will also address the joints that surround the fixator to prevent furthercontractures.Once surgery incisions are healed, a heated pool may be a good environment for therapy.The water’s property of buoyancy can decrease the pain that may occur with weightbearing. Aquatic therapy can also provide an environment where muscles can bestrengthened in a fun way with swimming.Once the patient’s goals are achieved and intense physical therapy is not required,transition planning will occur and recommendations for the home, work or school andcommunity will be provided. The development of a home exercise program willmaintain the gains that have been achieved through surgery and therapy and preventsecondary complications that are due to pain and immobility.Is Physical Therapy painful?Some activities that are performed in Physical Therapy can be uncomfortable because itis hard work. There are things that a therapist can do for their patient to make therapyand exercise more comfortable. Some examples of this are relaxation techniques such asdeep breathing and imagery. There are also modalities like heat and ice, which can easethe discomfort caused by exostoses or surgery. Music therapy has been shown to beeffective at decreasing pain in patients with other types of chronic pain (8).Are there other diagnoses that are associated with MHE and/ or MHE surgery?There are some neurological disorders that can be associated with MHE. These includeperipheral neuropathy and Complex Regional Pain Syndrome. (9,10,11) Secondarycomplications from these can also be addressed with Physical Therapy.Chapter Three 3 Section Two
  • 72. In peripheral neuropathy, the nerves that control the muscles are damaged due to beingcompressed by exostoses. This leads to a loss of nerve conduction to the muscle andresulting weakness in that muscle. It can affect the motor part of the nerve or the sensorypart of the nerve. Impairment can range from slight to complete. Because the nerves arenot central to the nervous system, they can regenerate once the compression is relievedsurgically. This is, however, a slow process. Physical Therapy can address this withstrengthening exercises and bracing, while the nerves to the muscles are healing. (9,10)Complex Regional Pain Syndrome, type I, (also known as reflex neurovascular dystrophy “RND”or reflex sympathetic dystrophy “RSD”) is a common condition characterized by extreme limbpain associated with autonomic dysfunction. This condition is associated with mild trauma to anextremity, as in the case of a painful exostoses or surgical removal of exostoses. In this situation,there can be temperature, hypersensitivity, and trophic changes to the effected extremity.Treatment of this disorder in adults ranges from medications, surgical sympathetic nervoussystem blocks and psychotherapy. In children, studies show the symptoms of this condition canbe controlled with physical and occupational therapy. Treatment for this includes de-sensitizationtechniques where various textures are applied to the affected area for prolonged periods of time.This usually begins with very light touching with cotton and progresses to different textures, suchas cloth and brushes. Weight bearing activities are also essential to retraining the sensory system.Progressing weight bearing to the patient’s tolerance is an important part of treatment. If weightbearing is restricted after surgery, deep pressure applied to the extremity in non-weight bearingpositions can be substituted, until partial weight bearing is allowed. Exercise is also an integralpart of treatment for complex regional pain syndrome and has been shown to be an effectivetreatment for this chronic pain disorder without the use of medications. (11)Note from The MHE CoalitionIt can be very disconcerting for parents to see a child with RSD experience the episodes of burning painassociated with this disorder. It is important to remember how important treatment for this disorder is, andto work with your child’s physical therapy team in designing a program that you can carry out at home. Inaddition to the normal range of exercises prescribed, there are beneficial “games” that the child can play,both at physical therapy and at home. If RSD is affecting the foot, fill a pan with play sand in which youhave buried some marbles and coins. Have the child put his foot in the pan and try to pick up the itemswith his toes. This can help with desensitizing the foot, and promote movement, which the child might beavoiding because of pain. Children also enjoy kicking balloons and lightweight balls, when they are able.Another game is to have the child pick up marbles with his toes and place them into a bowl or cup, and tryto beat the previous score each session the game is played. Appealing to the child’s spirit of competitionand fun can sometimes make the child forget that she is doing something therapeutic, and concentrating onthe “score” can sometimes lessen the discomfort of the exercises. By working with your child, you willalso discover the best way to handle episodes of pain. During some episodes, the child may not be able tostand touch, while at other times it may be necessary to apply firm pressure on the effected area.Is it safe for patients with MHE to participate in sports and recreation?Fitness and well-being is important for everyone, including the patient with MHE. Everyopportunity for continuing exercise in a supervised manner should be encouraged. Sportsand physical education can often be safe to participate in with a doctor’s approval as longas the patient is being monitored by the orthopedic surgeon and physical therapist. Non-contact sports like swimming, cycling, dancing, tai chi, yoga and "Pilates" can be safeand fun forms of exercise for some patients with MHE. It is important to remember thatMHE affects patients differently and certain sports and recreational activities may not beappropriate choices for people whose range of motion is limited by hip, pelvis and lowerextremity exostoses. Additionally, if anyone with MHE experiences pain whileparticipating in sports or recreational activities, he/she should stop doing the activity andspeak with their doctor.Chapter Three 4 Section Two
  • 73. Some people with MHE tire very quickly when doing physical activity. Children withMHE need frequent rest breaks. Some children may be unable to participate fully in theirschool’s physical education class. In these cases, there are federal laws under theAmericans with Disabilities Act (ADA) and Individuals with Disabilities Education Act(IDEA), which entitle these patients to adaptations and accommodations and prohibitdiscrimination based on physical disability. Additionally, Physical Therapists can workwith schools to adapt physical education classes or provide alternative activities in orderto meet the curriculum’s health and physical education requirement.(34 C.F.R. § 300.26)Parents may also request a copy of their school district’s detailed physical educationcurriculum to review with their child’s orthopedic surgeon to determine if there are anyactivities planned which are medically restricted for the child. Some school districts haveallowed students to meet Physical Education curriculum requirements with speciallydesigned instruction like written work on Physical Education topics. While this may bean acceptable physical education substitution for some children with MHE who are verylimited in their physical mobility, it may be difficult for other children with MHE to doexcessive written work due to exostoses in their hands and wrist. Additionally, chronicfatigue issues can also prohibit some children’s ability to perform excessive writingactivities. Some school districts have accepted a student’s performance of the homeexercise program that has been instructed by his/her Physical Therapist as speciallydesigned instruction for meeting physical education curriculum requirements. AnIndividualized Education Plan (IEP) team will work with parents to ensure that the childis able to access curriculum requirements while addressing the child’s unique needs. (12)Physical Fitness is an individualized concept. There are many types of activities that canbe beneficial even if a person with MHE cannot participate in competitive or recreationalsports due to fatigue or mobility impairments. Options for fitness include adaptedwheelchair sports, seated aerobics and dance, and water aerobics. By encouraging asmuch independence as possible for a child in his/her school setting, he or she can get asignificant amount of physical activity from walking to and from classes, sitting throughclasses, and keeping up with their studies. Physical Therapists can work with patients todetermine their optimal activity level and options for fitness and well-being.Note from the MHE CoalitionMany children with MHE enjoy playing sports and taking gym. In some school settings,families discuss the child’s condition with the appropriate school and PE personnel, withthe understanding that the child should not be forced to “just try” or do any activity thatcauses pain or that the child knows may injure an area affected by exostoses. Otherchildren may have pain, fatigue and mobility issues that make any activity beyond thatrequired to get to their classes and do their school work impossible. Parents may have toact as advocates on behalf of their children in order to receive the best possibleaccommodations or modifications for their child’s Individual Education Plan. Yourchild’s doctors and physical therapists should be advised of any mobility, pain andfatigue issues, not only as regards treatment, but also so that they can be included in yourchild’s medical records. Medical and physical therapy reports are importantdocumentation in support of requested modifications.Chapter Three 5 Section Two
  • 74. CONCLUSION:An overview of Physical Therapy for patients with MHE has been provided; however,each patient is individual and not all Physical Therapy interventions are indicated for allpatients. All Physical Therapy should be patient and family centered in its approach.Exercise and fitness can be a family event and an activity that children, their siblings andparents can share to benefit each other.References:(1) Guide to Physical Therapy Practice. 2nd edition. Physical Therapy: 2001; 81:9 744.(2) Anthony KK, Schanberg LE. Juvenile Primary Fibromyalgia Syndrome. Curr Rheumatol Report.2001 Apr;3(2):165-71.(3) Klepper SE Effects Of An Eight-Week Physical Conditioning Program On Disease Signs And Symptoms In Children With Chronic Arthritis. Arthritis Care Res. 1999 Feb;12 (1): 52-62.(4) Han A, Robinson V, Judd M, Taixiang W, Wells G, Tugwell P. Tai Chi For Treating Rheumatoid Arthritis. Cochrane Database Syst rev. 2004; (3): CD004849H(5) Frost, JA Klaber Moffett, JS Mose, JCT Fairbank, Randomised Controlled Trial For Evaluation Of Fitness Programme For Chronic Low Back Pain. BMJ 1995; 310: 151-154 (21 January)(6) Varju C, Kutas R, Petho E, Czirjak L. Role Of Physiotherapy In The Rehabilitation Of Patients With Idiopathic Inflammatory Myopathies. Orv Hetil. 2004 Jan 4; 145 (1) 25-30.(7) Stanton-Hicks M, Baron R, Boas R, Gordh T, Harden N, Hendler N, Koltenzenburg M, Raj P, Wilder R. Complex Regional Pain Syndromes: Guidelines For Therapy. Clin J Pain. 1998 Jun; 14 (2): 155-66.(8) Standley JM, Hanser SB. Music Therapy Research and Applications in Pediatric Oncology Treatment. J Pediatric Oncol Nurs. 1995 Jan; 12 (1):3-8.(9) Paik NJ, Han TR, Lim SJ. Multiple peripheral nerve compressions related to malignantly transformed hereditary multiple exostoses. Muscle Nerve. 2000 Aug;23(8):1290-4.(10) Levin KH, Wilbourn AJ, Jones HR Jr. Childhood peroneal neuropathy from bone tumors. Pediatr Neurol. 1991 Jul-Aug;7(4):308-9.(11) Sherry D, Wallace C, Kelley C, Kidder M and Sapp.Short and Long termOutcomes of Children with Complex Regional Pain Syndrome type I Treated withExercise Therapy. J Clinical Pain. 1999 15 (3): 218-223 (12) Department of Educaton. Rules and Regulations Federal Register/Volume 64. No 48/Friday, March 12, 1999.Chapter Three 6 Section Two
  • 75. Chapter Three: Living with MHE Section Three Products and Ideas to Help Make Living with MHE a Little Easier Contributor: Susan WynnReprinted from The MHE Coalition Newsletter No. 17, December 2004
  • 76. Products and ideas to help make living with MHE a little easier… Susan Wynn Reprinted from The MHE Coalition Newsletter No. 17, December 2004Living with MHE can present a wide array of challenges. Some of these challenges maybe temporary, following surgery or during periods of flare-ups. Some of these challengesmay be life long. Exostoses can create problems with mobility, range of motion, finemotor skills, and cause pain and fatigue that may affect the performance of daily tasks.While surgery, physical therapy and pain management may help some people with someof these issues, for the most part there is no way to remove the cause of the difficulty.Therefore, it is important for the person with MHE to find solutions to some of thesebasic problems, and fortunately there are many products available that can help.Assistive devices are nothing new. They are used by the elderly, by people of all ageswith arthritis, by joint-replacement patients during recovery. According to The NewYork Arthritis Reporter, “These tools are not only helpful to get a certain job done, theyare also essential to preserving the integrity of joints already compromised….Anotheradvantage they offer is the ability to maintain the user’s independence in performingeveryday activities, from personal hygiene to household chores and work-related duties.”Some of these devices can be very beneficial to MHE patients.All of the items described in the following sections can be found through the sourcesmentioned throughout and in the resource section. These catalogs and websites containmany additional products and ideas, and are worth looking through for suggestions toindividual problems, as well as to compare similar items and prices.DRESSING AND GROOMINGChallenges:A person may have trouble putting on shoes or socks, or cutting toe nails because of shortor bowed forearms, or because hip or leg exostoses make bending difficult. A personwith limited range of motion in shoulders may have difficulty brushing or blow dryinghair. Exostoses in fingers and hands can affect one’s ability to button or tie.Solutions:There are many assistive devices available to help with these difficulties. There areseveral varieties of sock aids available for those who either cannot reach their feet or whohave weak grasps. As a teenager looking for independence, Nicole recently began usingthe Sock-Assist with good results. Nicole says it takes a little time to get the socks on, butit does work. There is also a Pantyhose Aid available. Extra long shoehorns eliminate theneed to bend over when putting on shoes, and a Shoe Remover is available to help takeoff shoes, also without bending over. For those who have difficulty tying shoes, slip onshoes are wonderful, but if you want to wear shoes that tie, shoelaces, such as Coilers, areavailable with coils that never need tying, or there are deluxe elastic shoelaces that allowshoes to be slipped on and off without tying and untying. DressEZ makes a combinationChapter Three 1 Section Three
  • 77. Long Handle Shoehorn and Dressing Aid. For those who have trouble reaching, dressingsticks are available, and for those who have trouble with their hands, Zip Grip snaps ontozippers to extend pull tabs, and Good Grips makes a button hook.Long handle toenail scissors help those with limited reach, and there is a universalextension holder available that you can attach a razor to for shaving legs. There are alsolong handle brushes, combs, back scrubbers and sponges to help those with limitedshoulder ROM. Nail Clipper Boards and nail brushes are available on bases with suctioncups to attach to sink, making their use much easier for those with hand problems. Ahairdryer holder makes styling hair easier. Also important are items that address safetyconcerns, such as bathtub safety rails, bath or shower benches/seats, and grab bars.MOBILITYChallenges:Mobility issues can fall into two categories: dealing with mobility problems followingsurgery, and dealing with problems caused by exostoses, chronic pain and/or fatigue, orlimb length discrepancies, including inability to walk for long distances or stand for longperiods.Solutions:For postoperative patients, there are different solutions available depending upon the typeof surgery and the patient’s ability (or inability) to walk. For some, a wheelchair will benecessary, while others may use walkers or crutches while they are non-weight bearing orpartial weight bearing. It is a good idea to have a preoperative physical therapy sessionto get familiar with the type of mobility aids you will be using following surgery. It isrecommended that patients with exostoses under their arms try crutches out beforesurgery to see if they are a comfortable option. If not, arrangements should be made forthe patient to use a walker.For those suffering with chronic and severe fatigue and/or pain, wheelchairs may benecessary where prolonged periods of walking or standing will be taking place. Formany, canes can provide sufficient support during mobility. There are many differenttypes of canes which provide specific solutions. For instance, the Sport Seat( converts from a walking stick toa seat, which can be extremely helpful if legs are giving out and there isn’t a bench insight. Folding canes are available, which are lightweight and easy to store. Nicole keepshers in her backpack in case she has a problem at school and needs help getting around.There is a product called “Portable EZ-Step” ( thatclaims to reduce pain of stair climbing and makes stairways easier to go up and down. Ifanyone tries this product, we’d be interested in hearing your opinion.COOKING, CLEANING, AND EVERYDAY CHORESChallenges:The combination of pain and fatigue, inability to bend down or reach up, weakness orpain in hands or wrists, can make cooking and cleaning difficult.Chapter Three 2 Section Three
  • 78. Solutions:The catalogues and web sites in the resource section have large selections of utensils thatmake kitchen work easier for those with hand and wrist problems. Good Grips makes awide selection of products that are easy on the hands, from an ergonomic, natural gripbread knife to bottle and can openers, vegetable peelers, and scissors. Cutting boards,pan holders, and a “spreadboard” bread holder are available to allow for one-handed usewithout danger of things sliding away from you while you’re cutting, stirring or makingsandwiches. There are many different options for opening jars, from the under-cabinetopeners recommended by Audrey, to electric jar openers, and there are devices to helpwith pull-tabs.Just as there are products to help with grooming, there are products to help people withdifficulty bending clean their homes. Brooms and dustpans and sponges are all availablewith long handles. Grabbers are an extremely helpful tool for picking things up off thefloor or reaching things high up on shelves. There are several brands available, but Alidaswears by the Golder Retriever Reacher (available at as well as othersites). The Roomba and other robotic vacuums can be a big help for someone who hasdifficulty managing regular vacuuming.Other aspects of day-to-day life can be problematic when exostoses affect fingers andhands. Products such as grips for keys and for turning small handles, as well as handledoor knob adaptors can help.GARDENINGChallenges:Pain and fatigue, difficulty bending and kneeling, reaching, and difficulty using regulargardening tools due to hand pain, mobility and rotation.Solutions:Catalogs, such as Life with Ease ( offer a wide range ofergonomically designed gardening tools to help prevent hand and wrist injury, availablewith regular and long handles. Special rakes, shovels, pruners, hoes and other tools areall available. There is also an arm support with add-on handles that allows you to useregular tools and appliances with greater ease. Garden scoots, kneeler-stool combinations,and a lightweight foldaway wheelbarrow are all useful.SITTINGChallenges: Exostoses in the hip, pelvis and femur can affect ability to sit comfortably. Hardsurfaces can put pressure on exostoses, causing pain. It can be difficult, if not impossible,to get down and sit on the floor, and difficult to get back up.Chapter Three 3 Section Three
  • 79. Solutions:There are several cushions on the market which can make sitting much more comfortable.The Therapy Shoppe Catalog ( has several available. Julie’sfive-year-old son uses the “Disc’O Sit”, and Nicole, a high school sophomore, uses theFit-sit Cushion. Not only do these cushions relieve pressure on exostoses, but they alsoaddress fidgeting and fatigue issues. These cushions can be used on the floor as well ason chairs. If you need help getting out of your chair, there is a self-powered liftingcushion to provides a boost, and there are chairs that contain actual lifts to help lower youdown, recline, sit up and then rise to almost standing position ( getting in and out of the car; difficulty pressing on gas and accelerator. It canbe difficult to open the gas cap.Solutions:Nathalie is applying for funding to have an accelerator placed on the steering wheel, asdriving is painful for her. She’ll let us know how this goes! There is a swivel seat tohelp you sit and swivel your legs into and out of a car, and there are hand bars that aresecured to the frame of the car door that offer stability when getting in and out of a car.A Universal Grip can be used to help open the gas cap.SLEEPINGChallenges:As with sitting, lying down puts painful pressure on exostoses. For many with MHE, agood night’s sleep is impossible. It can also be difficult getting out of bed.Solutions:Fortunately, there are many new mattress options that offer some relief. Chris uses asleep number bed (an air mattress that you can control the firmness of), with a Tempur-pedic mattress topper. ( Nicole uses the Versailles memoryfoam mattress set and pillow from Dormia (, which works better thananything else she has ever tried. Christina recommends the True Sleeper mattress topper,which is more economical than Tempurpedic and Dormia ( Search forTrue Sleeper). In Karla’s house, three family members with MHE use three differentsolutions: One uses a water bed because of bowing and nerve damage to legs, one uses awater bed with lots of pillows for legs and back, and one uses an inexpensive memoryfoam mattress topper from Target ( Search for Memory foam mattresstopper). There are many different versions of the memory foam mattress toppers andmattress sets available, in many different price ranges. Most everyone we asked does usea lot of pillows to cushion bumpy bones somewhere on their body, no matter what type ofmattress they use.Chapter Three 4 Section Three
  • 80. Julie’s son uses a down comforter with fleece on one side for extra softness and warmthwithout extra bulk or weight, which is also an important consideration. Julie’s friendmakes duvet covers for her children out of sheets, thereby eliminating the sheet part ofmaking the bed. Since the cover is sheets, they can sleep under one piece without gettingwrapped up in extra layers of cover and weight, the covers can easily be removed andwashed, and it makes it easier for kids to make their beds. Deena recommends bodypillows from Gaiam – A Lifestyle Company ( The pillows are inwholly organic cotton covers that feel very good. Also available are cushions for lumbarsupport, and gel wraps with cotton covers for pain relief and neck support. For anyonewho has difficulty getting out of bed, there are various types of bed pull-ups, bed canes,and handle systems to help make getting up easier. There is also a leg lifter to help raiseor lower legs without bending over.WRITING, KEYBOARDINGChallenges:Hand and wrist pain makes writing painful and difficult.Solutions:For those who have an extremely difficult time keyboarding, Nathalie recommends acomputer program that allows you to dictate to your computer, “Dragon NaturallySpeaking.” The latest version is supposed to be much better than previous versions.While Nathalie says it does take time to learn the commands of how to use the program,it provides the wonderful opportunity of being able to work without typing. For thosewho have pain when writing, there are many pens and pencils now available on themarket designed to be more comfortable to hold. There are also grips available to usewith regular pens and pencils. Many students use an Alphasmart keyboard, aninexpensive alternative to a laptop computer ( New technologyprovides wrist and hand rests for computer users, and better mouse design.( There are many products including braces, heat andice packs that can help during painful flare-ups.There are many other products, too numerous to list here, that make life for thosewith MHE and other musculoskeletal diseases easier and more productive. If youhave recommendations for products that help make your life easier, please let usknow. The MHE Coalition does not endorse any of these products. As ourdisclaimer states, while many find the information and experiences that we sharehelpful, they are in no way a substitute for professional medical care. We do not, asan organization, support or endorse any particular treatment, therapy ormedication. However, we hope that these ideas will encourage you to investigatethe many products that are available.Chapter Three 5 Section Three
  • 81. RESOURCESThe products listed above are available from a variety of sources, and it is a goodidea to shop around and compare items and prices.Dynamic Living, Inc., 1-888-940-0605, www.dynamic-living.com428 Hayden Station Road, Windsor, CT 06095 (print catalog available)Functional Solutions, 1-800-235-7054, www.BeAbleToDo.comNorth Coast Medical, Inc., 18305 Sutter Boulevard, Morgan Hill, CA 95037-2845 (printcatalog available)Life with Ease, 1-800-966-5119, www.lifewithease.comP.O. Box 302, 435 Rt. 103, Newbury, NH 03255 (print catalog available)The Therapy Shoppe, 1-800-261-5590, www.TherapyShoppe.comP.O. Box 8875, Grand Rapids, MI 49518 (print catalog available)Alphasmart, www.alphasmart.comThe Arthritis Foundation,, Product and Services DirectoryDormia, www.dormia.comGaiam, www.gaiam.comThe Golden Retriever Reacher, 1-800-745-9558, www.badback.comPain, www.painreliever.comTempur-pedic, www.tempurpedic.comWalking Cane Depot, 1-888-399-4870, www.walkingcanedepot.comThe Wright Stuff, Inc., Athritis Supplies, www.arthritissuplies.comMany thanks to all those members of the MHE Yahoo Online Support Groupwho shared their product recommendations and ideas.Chapter Three 6 Section Three
  • 82. Chapter Three: Living with MHE Section Four Preparing for Your Next Medical AppointmentReprinted from The MHE Coalition Newsletter No. 16, June 2004
  • 83. Preparing for Your Next Medical Appointment Reprinted from The MHE Coalition Newsletter No. 16, June 2004Whether the patient is your child or yourself, you are an important part of a health-careteam. Together with the orthopaedist treating you and/or your child, your team may alsoinclude physical therapists, occupational therapists, pharmacists, pain specialists, x-raytechnicians and others involved with the ongoing treatment of MHE. During a doctor’sappointment, it’s easy to get sidetracked. Anxiety often runs high and can block yourclearest thinking. Doctors have schedules to keep and are often pressed for time. If youfeel pressured during the appointment, it may be difficult to stay focused on addressingeach of your concerns. Maximize your time with the doctor by preparing for yourappointments beforehand. Here are a few suggestions for making the most of your nextappointment. If seeing a new doctor, or if you are having several problems that need to be addressed, tell the office when you call for an appointment that you will need sufficient time to talk to the doctor. If you or your child is a new patient, arrange to have medical records and x-rays transferred to the new physician before the appointment. Write down your questions and then prioritize them. For instance, put a #1 by the most important, #2 by the next most important, etc. Start by asking the doctor the most important question first, then the next most important, and so on. Stay focused on your questions. If you wander into interesting side stories you will lose valuable time. When you arrive for the appointment, give the medical assistant a copy of your written questions and ask that they be put on the front of the chart so the doctor can see them. If possible, have someone come with you into the exam room. This person should also have a copy of the questions. He or she can take notes during the appointment and help make sure your questions have been addressed to your satisfaction. Bring all your medications with you to the appointment. Let your doctor know all the over-the-counter medications you are taking and how much. If you hear words you do not understand, ask for an explanation. Doctors are used to using medical terms and sometimes forget that it includes words the rest of us do not understand. If the doctor does not have enough time, ask if someone else on his / her staff can answer your questions. Remember, you have a right to have your questions answered.Chapter Three 1 Section Four
  • 84. When a surgery is recommended, ask about the benefits and the risks, as well as any alternatives. Ask your doctor about pain management after surgery, as well as pain management after release from the hospital. Ask your doctor to show you the X-rays and have him/her explain the surgery showing you the X-rays. This way you can show the doctor pointing to the X-ray something you may not understand. Don’t be afraid to let your doctor know you don’t understand something. Spend time after the visit talking with the person who came with you. He or she will likely have good insights about the appointment and can help you identify any areas that are still unclear Ask the doctor to send a copy of his /her report to your home. Pain Issues can be better addressed by your doctor if you provide complete background information: If you have pain issues, you will want to fill out a pain diary. Make a copy of your pain diary to give to your doctor, so you can go over it together and the copy will be made part of your medical records. Include the following information: • Location(s) of your pain. • Description of your pain: sharp, stabbing, burning, nagging, stiff, throbbing, etc. • It’s helpful to also use a pain scale to describe your pain: 0 being the least amount of pain and 10 being the most amount of pain. • How long does the pain last? • How do you feel when you wake up? • What aggravates the pain? • When does pain start in the day? • What activities cause pain? • What is pain like at mid-day; what is pain like in the evening; what is pain like at night in bed? • Does pain wake you up? • Do you currently take medication for pain. If so, what do you take (name of drug, dosage) • Are there any other treatments that help relieve your pain (i.e. heat, ice, exercise, rest, etc.). • How long does it take to get pain relief after you take your medication? • Does pain come back before you are next scheduled to take your medication? • Does driving affect your pain? • What activities are you unable to do because of pain? • How does your job (or school) affect your condition? • Watch to see if any patterns develop and let your doctor know. You may also want to fill out a bumpy bone tracker and a pain tracker, which can both be printed from the MHE and Me website. Print out a copy of the pain study summary off the MHE Coalition website and give it to your doctor.Chapter Three 2 Section Four
  • 85. Chapter Three: Living with MHE Section Five MHE Surgery: Some helpful tipsand advice from families who have been through itReprinted from The MHE Coalition Newsletter No. 10, June 1, 2002
  • 86. MHE SURGERY Some helpful tips and advice from families who have been through it Reprinted from The MHE Coalition Newsletter No. 10, June 1, 2002With several new members facing their children’s first surgeries, we decided that thiswould be a good time to revive the idea of an MHE Surgery Handbook. Starting thisproject on a small scale, I asked for input from YahooGroups members. Our thanks toJoAnn, Cassie, Kate, Karla, Max, Chele, and Suzanne for sharing what they have learnedthrough their children’s (and in some cases their own) surgeries. We would love to getmore tips for the MHE Surgery Handbook for both children and adults, including specifichints for different procedures (i.e., fixators, hip surgery, arm surgery, hand surgery, etc.).Please send them to me at, or by mail to 14 Stony Brook Drive,Pine Island, NY 10969. Thanks! Susan WynnPreparing for Surgery Find out everything you can about the surgery, hospital procedures before hand (Will you be allowed to accompany your child into the operating room and stay with him or her while anesthesia is being administered? How will anesthesia be delivered? Will you be allowed into the recovery room, and when? Will a parent be allowed to sleep in the child’s room, visiting hours, etc.). Don’t assume that every hospital allows the same level of parental participation. Knowing as many details as possible will help make you less anxious, and you’ll know that you’ll be able to keep promises that you make! A calm parent makes for a calmer child. If you are having difficulty dealing with your own anxiety, speak to your doctor about ways to handle it. Suzanne says the one thing that most helped her son, Bobby, prepare for surgery was the hospital tour. The entire family participated in a tour of the operating and recovery rooms, and Bobby got a first hand look at the table, the lights, and the equipment, receiving explanations of the procedures so that there was little left to the imagination and his fears were allayed. Several other parents have said that the pre-hospital tour is helpful for the whole family. Max advises families having surgery done at a large medical campus to look at a map and know where everything is before you go! It’s easy to get lost, especially when you’re anxious and feeling overwhelmed. JoAnn found a wonderful website that features “You’re Having Surgery! A preparation guide and coloring book for pediatric surgery”. This is available at There are books available to help kids of all ages deal with their anxieties about undergoing surgery. An MHE and Me favorite is: “Franklin Goes to the Hospital” by Paulette Bourgeois and Brenda Clark, and we try to send copies of both the book and coloring book, along with a stuffed animal, to young children scheduled for surgery whenever possible. If you are unable to make it to the hospital for a tour, there are online hospital tours available .Chapter Three 1 Section Five
  • 87. Karla has a tip to help make pre-ops go a little easier: Start drinking lots of water 2 or 3 days before going to the hospital to make veins nice and “plump”, so that pre-op blood work will go easier. If your child will need crutches, a walker, or a wheelchair after surgery, try to arrange for pre-surgical training. It is a big help if a child can learn to get around before he or she is experiencing post-operative pain. Have your doctor give you prescriptions for pain medication prior to the surgery, so that you can have it filled and waiting for you at home when you arrive back from the hospital. Most children only need prescription pain medication for a few days. Cassie recommends speaking to your doctor about “layering” Tylenol with Motrin after surgery, which means giving Motrin or Tylenol, then a specified number of hours later giving the other. As always, be sure to check with your child’s physician about any medications. Cassie also recommends stocking up on Benadryl, for the itchies that often seem to occur after surgery. Will your child be in a cast or an immobilizer after surgery? Before surgery is a good time to try ways to get in and out of the car, up and down stairs, etc. Wrap your child’s leg or arm in a big towel, then playact how you will be able to accomplish these normally easy acts. This is something we wish we had thought of before Nicole’s first surgery. The logistics of getting in and out of the car, then having to carry her into the house were just things that never occurred to us, and it was very, very difficult. We’ve gotten much better with practice, and Nicole is great at figuring out alternate methods of mobility. A pre-surgery shopping list might include items like: flushable wet wipes (sometimes a bedpan is necessary for a day or so…), disposable, rinse-free cloths (like Comfort Bath), which you can heat in the microwave (they now also make a special cap for a water-free “shampoo, too). Kate suggests liquid shower gel, since regular soap is too hard to rinse off in a sponge bath. Ginger ale or coke, Popsicles, Jello, crackers, etc., in case your child is queasy, something that can last for several days after surgery. Loss of appetite is common, and can last for awhile. Meal replacement drinks can be helpful, if your child will take them. Cassie recommends bags of frozen peas to use as icepacks after surgery. (Just be sure to mark the bag. Since it will be in and out of the freezer, you won’t want to cook them). Another handy item for when you’re ready to use heat: socks filled with raw rice (not instant) and tied at the top are microwaveable and make great heat packs. Use different size socks for different areas! (Soccer socks can make great heat wraps for around the neck and shoulders!). Think ahead to what your child will wear home from the hospital. If you’re having arm surgery, Kate says that, since you won’t be able to pull things over your head, tops and pajamas that button are absolutely essential. If the leg will be in an immobilizer or cast, you will need wide leg, stretchy shorts or sweats that will fit over it, and loose-fitting socks and slippers can be of help, too. You’ll also need underwear that can fit over the bandages, etc., so make sure it’s stretchy enough!Chapter Three 2 Section Five
  • 88. Packing for the Hospital Karla’s list included some great ideas: Pack a disposable camera and get pre and post-op snapshots, plus photos of all the wonderful hospital staff. Have duplicates made and send the hospital a set, too! Bring a favorite movie to the hospital, labeled with own name. (Note: Double check with the hospital to make sure a VCR will be available for your child. Not all hospitals have them, as we found out when we went prepared with Nicole’s favorite tape). Bring a favorite soft blanket or pillow for cuddling with. Buy new soft slippers for your child’s hospital stay and give them as a surprise at the hospital. Cassie brings along her own feather pillow. Conor uses it when he needs it, either for comfort, or for extra propping, and Cassie uses it when Conor doesn’t need it. Cassie also brings along a supply of soda, and a book or video for her to watch for those times Conor’s sleeping. Make sure you have a pad and pen with you to write down any instructions the medical staff might give, and to write down questions you might have. Keep track of when pain and other medications are given and when your child will be due for the next dose. There are times when you will need to make sure your child gets his pain medication on schedule. You don’t want to wait until your child is hurting. Even if your child is scheduled for same-day surgery, it doesn’t hurt to throw into a bag, toothbrushes, toothpaste, a clean t-shirt, and other essential items, just in case it turns into an overnighter. Bring along a few snacks. You may not be able to get away for meals. Also pack any medications you might need, for headache, backache, etc. The experience can be both emotionally and physically stressful.The Ride Home agrees – bring plenty of pillows for the car, for the ride home. You’ll want to cushion the area operated on, and make the patient as comfortable as possible. Another helpful item is a small plastic garbage can and some plastic liners, just in case your child gets sick on the way home. Keep some towels and wet wipes in the car, too. Chele has plenty of experience here and, besides collecting all bed pillows in the house, advises that driving home, take it slow, avoid railroad tracks, and time your departure after your child has had pain medication and it has begun to take effect. Even though it can be difficult, be sure to use the seatbelt!When you Get Home If possible, have someone set up the bed for the patient so it’s all ready for your arrival. We usually have Nicole sleep on the living room couch for a few days post- op. It’s a good height for her, and there is an easier path for her to get to the bathroom with her walker. There is also room there for me and her younger sister to camp out with her. We have the couch covered in several soft quilts, plenty of pillows, and that same plastic garbage can nearby, as nausea can continue for several days post-op. I usually wind up sleeping near Nicole for several days post-op. Depending on the recuperation and type of surgery, parents have been known to “camp out” for much longer periods.Chapter Three 3 Section Five
  • 89. According to Chele, the day you come home from the hospital, and the next day, are the worst, so be prepared. She also advises that it will probably be between 5 and 7 days before you get a full night’s sleep, so nap when your child naps, sleep when your child sleeps, and have plenty of coffee on hand! The first few days post-op, make sure that pain medications are given on schedule. Once pain starts, it’s harder to control. Remember that this is a hard time for siblings, who are bound to feel frightened when they see their brother or sister in pain, and left out and forgotten when their needs have to take a backseat to a post-op patient.Chapter Three 4 Section Five
  • 90. Chapter Four: MHE and Pain Section One Hereditary Multiple Exostoses and Pain Abstract of Study Published in Journal of Pediatric OrthopaedicsContributors: Sandra Darilek, MS, Catherine Wicklund, MS, Diane Novy,PhD, Allison Scott, MD, Michael Gambello, MD, Dennis Johnson, PhDand Jacqueline Hecht, PhD
  • 91. Hereditary Multiple Exostosis and Pain Sandra Darilek, MS,* Catherine Wicklund, MS,† Diane Novy, PhD,‡ Allison Scott, MD, § Michael Gambello, MD, PhD, *Dennis Johnston, PhD, and { Jacqueline Hecht, PhD*Abstract:This study was undertaken to characterize pain in individuals with hereditary multipleexostosis (HME). Two hundred ninety-three patients with HME completed aquestionnaire designed to assess pain as well as its impact on their life. Eighty-fourpercent of participants reported having pain, indicating that pain is a real problem inHME. Of those with pain, 55.1% had generalized pain. Two factors were found to beassociated with pain outcome: HME-related complications and surgery. Individuals whohad HME-related complications were five times more likely to have pain, while thosewho had surgery were 3.8 more likely to have pain. No differences were found betweenmales and females with respect to pain, surgery, or HME-related complications. Theresults of this study indicate that the number of individuals with HME who have pain hasbeen underestimated and that pain is a problem that must be addressed when caring forindividuals with HME.Key Words: hereditary multiple exostosis, pain, exostoses, osteochondromas, supportgroup(JPediatrOrthop2005;25:369–376)From*Department of Pediatrics, University of Texas-Houston Medical School,Houston,Texas; †Department of Obstetrics, Gynecology, and Reproductive Sciences,University of Texas-Houston Medical School, Houston, Texas; ‡Department ofAnesthesiology, University of Texas-Houston Medical School, Houston, Texas;§Shriners Hospital for Children, Houston, Texas; and Department of Biomathematics, {University of Texas, M.D.Anderson Cancer Center, Houston, Texas.Study conducted at the University of Texas Health Science Center, Houston, Texas.The MHE Coalition ( provided partial funding for this study. None of the authors received any additional financial support.Reprints: Jacqueline T.Hecht,PhD, Department of Pediatrics, University of Texas- Houston Medical School, P.O.Box 20708, Houston,TX 77225-0708 (e-mail © 2005 by Lippincott Williams&WilkinsChapter Four 1 Section One
  • 92. Chapter Four 2 Section One
  • 93. Chapter Four: MHE and Pain Section Two American Pain Foundation Pain Action GuideContributor: Reprinted with permission of The American Pain Foundation
  • 94. Pain Action Guide © 2001 American Pain Foundation 201 N. Charles Street, Suite 710, Baltimore, Maryland 21201-4111 Used by permission of The American Pain Foundation For more information, please visit their web site at, or call 1-888-615-PAIN Pain Care Bill Of Rights As a Person with Pain, You Have:The right to have your report of pain taken seriously and to be treated with dignity and respect by doctors, nurses, pharmacists and other healthcare professionals. The right to have your pain thoroughly assessed and promptly treated. The right to be informed by your doctor about what may be causing your pain, possible treatments, and the benefits, risks and costs of each. The right to participate actively in decisions about how to manage your pain. The right to have your pain reassessed regularly and your treatment adjusted if your pain has not been eased. The right to be referred to a pain specialist if your pain persists. The right to get clear and prompt answers to your questions, take time to make decisions, and refuse a particular type of treatment if you choose. Although not always required by law, these are the rights you should expect, and if necessary demand, for your pain care.How serious is the pain problem?Pain is a major healthcare crisis in the United States. More than 50 million Americanssuffer from chronic pain caused by various diseases and disorders, and each year another25 million experience acute pain as a result of injury or surgery.Although most pain can be relieved or greatly eased with proper pain management, thetragedy is that most pain goes untreated, undertreated, or improperly treated. No oneshould have to suffer needlessly when the knowledge and skills are available today tomanage most pain.If left untreated, chronic pain can prevent you from having a full and meaningful life.Once your pain is under control, your body and mind will be less stressed. Youll be ableto sleep better, focus on work, enjoy relationships with family and friends, and take partin social activities. If your pain has been caused by an injury or surgery, your recoverymay be faster once your pain is managed.Finding good pain care and taking control of your pain can be hard work. Learn all youcan about pain and possible treatments. Be persistent, insist on your rights, and dont giveup.Chapter Four 1 Section Two
  • 95. If most pain can be eased, why do so many people with pain sufferneedlessly?Many of us have beliefs about pain that are simply not true and prevent us from gettingthe relief we deserve. The truth is:Pain is not something you "just have to live with." Treatments are available to relieveor lessen most pain. If untreated, pain can make other health problems worse, slowrecovery, and interfere with healing. Get help right away, and dont let anyone suggestthat your pain is simply "in your head."Not all doctors know how to treat pain. Your doctor should give the same attention toyour pain as to any other health problems. But many doctors have had little training inpain care. If your doctor is unable to deal with your pain effectively ask your doctor toconsult with a specialist, or consider switching doctors.Pain medications rarely cause addiction. Morphine and similar pain medications,called opioids, can be highly effective for certain conditions. Unless you have a history ofsubstance abuse, there is little risk of addiction when these medications are properlyprescribed by a doctor and taken as directed. Physical dependence-which is not to beconfused with addiction-occurs in the form of withdrawal symptoms if you stop takingthese medications suddenly. This usually is not a problem if you go off your medicationsgradually.Most side effects from opioid pain medications can be managed. Nausea, drowsiness,itching, and most other side effects caused by morphine and similar opioid medicationsusually last only a few days. Constipation from these medications can usually bemanaged with laxatives, adequate fluid intake, and attention to diet. Ask your doctor tosuggest ways that are best for you.If you act quickly when pain starts, you can often prevent it from getting worse.Take your medications when you first begin to experience pain. If your pain does getworse, talk with your doctor. Your doctor may safely prescribe higher doses or changethe prescription. Non-drug therapies such as relaxation training and others can also helpgive you relief.How do I talk with my doctor or nurse about pain?1. Speak up! Tell your doctor or nurse that youre in pain. It is not a sign of personalweakness to tell them about your pain. Pain is a common medical problem that requiresurgent attention. So dont be embarrassed or afraid to talk about it.2. Tell your doctor or nurse where it hurts. Do you have pain in one place or severalplaces? Does the pain seem to move around?Chapter Four 2 Section Two
  • 96. 3. Describe how much your pain hurts. On a scale from 0 to 10, zero means no pain atall and 10 means the worst pain you can imagine. In the past week, what was the highestlevel of pain you felt? When did you feel it? What were you doing at the time? When didit hurt the least? How bad does it hurt right now?4. Describe what makes your pain better or worse. Is the pain always there, or does itgo away sometimes? Does the pain get worse when you move in certain ways? Do otherthings make it better or worse?5. Describe what your pain feels like. Use specific words like sharp, stabbing, dull,aching, burning, shock-like, tingling, throbbing, deep, pressing, etc.6. Explain how the pain affects your daily life. Can you sleep? Work? Exercise? Areyou able to do activities with family and friends? Can you concentrate on tasks? How isyour mood? Are you sad? Irritable? Depressed? Do you feel unable to cope?7. Tell your doctor or nurse about past treatments for pain. Describe any medicaltreatments youve had such as medication or surgery, and mention other approachesyouve tried. Have you done massage, yoga or meditation? Applied heat or cold to thepainful areas? Exercised? Taken over-the-counter medications, or supplements such asvitamins, minerals, and herbal remedies? Tried other treatments? Explain what workedand what didnt.Tip: Write down your questions for the doctor or nurse before an appointment. Peopleoften get nervous and forget to ask all their questions. Take notes so you can review themlater. If possible, bring along a family member or friend to provide support, help takenotes, and remind you of what was said.How can I get the best results possible?Take control. Its your responsibility to tell your doctor youre in pain, take part inplanning your treatment, follow your pain management plan, ask questions, and speak upif treatment isnt working. If necessary, seek other help. Be persistent until you find whatworks best for you.Set goals. Once youve found a doctor you trust, decide with your doctor on somerealistic goals for things you most want to do again - for example, sleeping, working,exercising, enjoying sexual relations, etc. Begin working on the easiest goals first.Work with your doctor or nurse to develop a pain management plan. This mightinclude a list of medications, when to take them, and possible side effects. It mightinclude therapies other than medication. Make sure you understand the plan and carry itout fully. If you dont, you are less likely to get relief.Keep a pain diary. Write down information about your level of pain at different times,how youre feeling, and what activities youre able to do or not do. Keep a record ofmedications youre taking or any non-drug treatments. The diary will help you see whatsworking and measure progress. Bring your diary on visits to the doctor.Chapter Four 3 Section Two
  • 97. Ask your doctor or nurse about non-drug, non-surgical treatments. These couldinclude relaxation therapy, exercise, massage, acupuncture, meditation, application ofcold or heat, behavioral therapy, and other techniques.Ask your doctor or nurse about ways to relax and cope with pain. The way you feelabout your pain can actually affect the pain itself. Your pain may feel worse if you arestressed, depressed, or anxious.If you have questions or concerns, speak up. If youre worried about medications orother treatments, ask your doctor or nurse. If your treatment is not working, insist thatyour pain be reassessed and new treatments offered. Be polite, but be firm.If youre going to have surgery, ask your doctor for a complete pain managementplan beforehand. Ask what medications you will receive before the operation tominimize pain later, and what will be available for pain relief afterwards.If youre a patient in a hospital or other facility and youre in pain, speak up. Ask adoctor or nurse for help. If you dont get help right away, ask again. If you still dont gethelp, ask to speak to the patient advocate or representative. Most likely the doctor ornurse will respond, but be sure to insist on effective pain care without delay.Pace yourself. Once you experience some degree of control over your pain, dont overdoit. Your body may be out of condition if you have been suffering pain for awhile. Taketime to gradually build up to normal activity.If youre not satisfied with your pain care, dont give up. Does your doctor listen toyou? Is your doctor able to assess and treat your pain? Are you getting adequate care? Ifafter a reasonable time the answer is "no," find another doctor or pain care program.Chapter Four 4 Section Two
  • 98. Chapter Four: MHE and Pain Section Three Evolving Views on Opioid Therapy for the Management of Chronic Pain. Pain Killers (Analgesics): Panacea, Poison or Somewhere in BetweenContributor: Richard B. Patt, M.D., President and Chief Medical Officer,Patt Center for Cancer Pain & Wellness, Houston, TX; Inpatient MedicalDirector, Hospice, Texas Medical Center; Co-author, You Don’t Have toSuffer (Oxford, 1994). Reprinted from The MHE Coalition Newsletter No.8, December 1, 2001
  • 99. Evolving Views on Opioid Therapy for the Management of Chronic Pain Pain Killers (Analgesics): Panacea, Poison or Somewhere in Between Richard B. Patt, M.D.What are opioids?There are at least two important ways to answer this question. Unfortunately, the mostscientific definition, while straightforward, is so disarmingly simple, that it doesnt tell usnearly all of what we need to know about these medications, because it ignores theimportant cultural forces that influence our use of these medications: the opioidscomprise a class of medications that have been employed to relieve pain for well overone hundred years. Their use is so routine in certain settings (after surgery, in theEmergency Room, for labor and delivery, for cancer and in the laboratory) that they areregarded as the standard against which all other pain-killing drugs (analgesics) arecompared. These drugs, previously referred to as "narcotics" are derived from or arechemically related to opium, the main constituent of the poppy plant (papaversomniferum), which has been used as a pain killer since biblical times. Science has onlyrecently demonstrated that the human body makes substances that possess a similarstructure and function. These endorphins, enkephalins and other molecules, referred to as"endogenous opioids," are thought to be responsible for the so-called "runners high."While the above explanation is accurate, it does not even begin to portray the ragingcontroversy that exists surrounding the contemporary use of opioids. While the term"opioid" is awkward at first, it is preferred to the term "narcotic." Contemporaryauthorities including the authors of our most important pharmacology textbook,Goodman and Gillmans The Pharmacologic Basis of Therapeutics have advised that weabandon the term narcotic. It is so culturally and socially laden with references to drugabuse that its use has a chilling effect on prescribers and patients alike, interfering withappropriate treatment of pain. The lurid images of back alley abuse conjured by the termnarcotic eclipse its scientific meaning, and as a result, the term opioid is stronglypreferred.In the midst of the tremendous progress that has been made generally in medicine andspecifically in our understanding of pain and its treatment it is practically unthinkablethat the individual who has done the most to advance our thinking about this issue is JackKevorkian. It has taken, arguably a fanatic, if not a lunatic (this authors thoughts) tobring to our attention that despite the most sophisticated health care delivery system inthe world, many Americans inappropriately are led to seek an early death because theirpain is not adequately addressed. Since medical science is by no means perfect, thosewho suffer are not necessarily entitled to relief of their pain, but they are certainly at leastentitled to our best efforts to achieve improvement, and by no means should they besubjected to humiliation or derision for seeking the relief of suffering. Although whenignored, unrelieved pain like any other chronic illness leads to depression, pain is almostalways fundamentally a medical problem, so we should no more coerce the sufferer to"tough it out" than we would encourage a diabetic to withhold taking their insulin as ameans to "build their character." While we dont readily admit it, modern medicineactually cures very little of todays maladies: diabetes and hypertension are noteradicated, but are managed, and thus the mandate to manage chronic pain over aChapter Four 1 Section Three
  • 100. patients lifetime should not be a surprise or a dilemma that we, as a culture, shouldshrink away from. These unfortunate individuals should certainly not be discarded ashaving "failed" our current treatments, rather we should acknowledge the shortcomingsof current therapies. It is only recently that pain in patients with life threatening cancerhas been treated more effectively, and although legislation exists to protect the rights ofthose with chronic pain (and the prescribing physician), in reality, one practically needsto be dying in this country in order to be assured of getting adequate pain relief.Can opioids (narcotics) be used effectively to treat chronic pain?Ive already indicated that the use of opioids is controversial in essentially all settings.Debate still persists about medicating terminal patients, so you can imagine how heatedthe discussion becomes for treating chronic pain, a setting in which there is no end insight and where complaints often appear to be out of proportion to accompanyingphysical signs or x-ray findings. Regrettably, most of todays cure-oriented physiciansstill do not understand chronic pain. Since it has only been recently that, stimulated byhordes of frustrated patients, a few physicians have even developed the courage to askquestions about chronic pain and opioids, it is not surprising that answers are still elusive.This question is actually probably best regarded as two related questions: (1) are opioidseffective in relieving chronic pain, and (2) if so, when (if ever) is their use appropriate?The bad news is that the ultimate answer to whether opioids are effective in the long termwill only be answered with certainty with controlled clinical trials which have not evenyet been proposed. Since it would be unethical to allow patients to suffer while awaitingthis data, we need to be asking what is known that will help guide todays treatmentsafely?The good news is that there has been increasing experience with using opioids to treatchronic pain due to a variety of causes. While still not as reliable as a controlled trial,data from this experience can be cautiously applied to many of todays patients withchronic pain. It appears that opioids effectively reduce pain over long intervals in aproportion of patients with chronic pain without intolerable side effects or problems withaddiction. One key point here is that as long as the source of pain persists, pain can oftenbe reduced but rarely if ever is it eliminated. Thus, if treatment is to even have a chanceat success, patients must maintain realistic expectations, such as a 50% reduction in painseverity. Another key point relates to side effects: in fact, most patients will experienceside effects when opioids are first started or their dose is changed, but when medicationsare started in low doses, are only gradually increased, and with reliance on long-actingformulations side effects can usually be resolved or minimized. Most patients willcontinue to experience low level side effects as long as opioid therapy is ongoing, but thismay represent a reasonable tradeoff if pain is severe. While opioids may producedangerous respiratory depression when used erratically, this almost never occurs withcarefully supervised use. Nausea, sedation and itch are common at first, but usuallyresolve over time. Constipation is an ongoing difficulty that can and must be preventedwith activity, diet and regular gentle laxative use. Because fatigue so commonlyaccompanies chronic pain, most patients cannot tolerate high doses of opioids, and thusmust be satisfied with partial relief. In other words, while opioids are helpful in somecases, they dont eliminate chronic pain: patients continue to have ongoing, but lowerChapter Four 2 Section Three
  • 101. grade symptoms, with some good and some bad days. These drugs are not a panacea, butsimply represent one of the many tools at our disposal to help make chronic pain morebearable. Moreover, opioids are usually not a first line treatment, and work best whenintegrated with other drug treatments like antidepressants, anti-inflammatories, musclerelaxants and anticonvulsants, as well as with non-drug therapies like physical therapy,distraction and relaxation training.Addiction RevisitedIn considering the contemporary role of opioids it must be borne in mind that, althoughthese substances are subject to abuse, the intention for which opioids exist is thetreatment of pain. Far too often, the potential for abuse interferes with the appropriate useof pain medications for those in need. Although drug abuse is a compelling public healthproblem, allowing abuse potential to limit access to opioids for those with medicalillnesses is an unjust response. A useful analogy is our system of using checks to pay forpurchases which is circumvented when "bad" checks are "bounced," ---- but we dontrespond by banning checks as legal tender, a policy decision that would punish everyone.If you believe in a higher power, especially one that did not put us here to sufferunnecessarily, then we can reason that God gave us the opioids and their derivatives tobetter cope with pain and suffering. Unfortunately, as a culture we have been tragicallyineffective in distinguishing between drug abuse and the treatment of pain, and thus whenit comes to pain medications, it has been a classic case of a few bad apples ruining thingsfor the whole bunch: todays patients with pain have become the innocent victims of awar on drugs that should have nothing to do with them.Research consistently demonstrates that exposure to pain medications does not fosteraddiction. In fact, under-prescribing is more likely to fuel addictive behavior, becausepain is never relieved, and patients are left feeling abandoned, left to continually seekhelp that becomes increasingly elusive. With chronic treatment, patients may becometolerant or accustomed to the effects of opioids (thus requiring higher doses over time),and physical dependence (the onset of withdrawal or an abstinence syndrome whentreatment is abruptly stopped) may arise, but addiction, a reversible complication, isextremely rare, occurring in no more than a few per cent of patients exposed to analgesicsin the course of treatment. Tolerance and physical dependence are inevitable biologicconsequences of chronic opioid use, that are independent of the patients background,values and circumstances. The onset of tolerance and physical dependence are expected,are unrelated to addiction and are not problematic since they can be overcome by simplyadjusting doses of medications gradually. Addiction, which is the same as psychologicaldependence, is an infrequent outcome that is highly dependent on the patients priorhistory, experiences and values. Addiction involves compulsive, nonmedical use of drugsthat persists despite the presence or threat of physiologic or psychological harm, andindeed is a highly disruptive phenomena. Rare in otherwise well-adjusted individuals,exaggerated perceptions of its dangers causes a great many patients with legitimate painto be mistrusted and undertreated. Unfortunately, when pain is ignored, most otheraspects of healing (rest, mood, nutrition, energy and rehabilitation) also falter. Too often,we operate from the mistaken belief that simple exposure to painkillers producesaddiction, while in fact addiction appears to be much more person- and style-specific thansubstance-specific. Predisposition to addiction has much more to do with an individualsstyle of coping with adversity, stress and illness. Addicts are less functional as a result ofChapter Four 3 Section Three
  • 102. their drug use and become more isolated from the mainstream of life, family and work,while patients using drugs appropriately are consequently more functional, less isolated,and more prone to resuming activities they once avoided because of pain.In the course of twenty years of educating physicians and nurses, patients and theirfamilies, administrators and policymakers and other interested parties about painmanagement, the topic of addiction never fails to elicit great interest. As a means toconvey my thinking about this complex issue and especially the thorny distinctionbetween addiction and the treatment of painful medical disorders with drugs, I createdand have come to rely on a vignette that, by employing an analogy focuses our attentionin a way that may help us think more clearly about issues that appear bewilderinglycomplex but are perhaps more simple than they appear to be.So..heaven forbid, your teenage child or grandchild "borrows" the key to the family car,say a Ford Taurus, goes on to drink a six pack of beer and then wraps said car around atree. Fortunate enough to walk away from the event, employing another example ofadolescent logic, he/she draws the following conclusion: "Ford Taurus* are bad cars."The obvious corollary is that drugs, in and of themselves are neither "good" nor "bad,"although their use can produce dramatically opposed good or bad outcomes depending onhow they are prescribed, dispensed and taken ("driven," if you will). Our culture strivesto ascribe pat answers to complex phenomenon, and thus arises the oversimplistictemptation to denounce a substance as being responsible for a behavioral problem,because it is often easier than looking honestly at our own maladaptive behaviors. As wehave come to recognize the dangers of alcohol and tobacco, it becomes clear that theproblem of addiction transcends the domain of illicit drugs, and viewed from an evenbroader perspective we have come to recognize the hazards of addictions to activities asdiverse as gambling, risk-taking and sex.The recent media feeding frenzy condemning a newer opioid compound, Oxycontin is aprototypic example of how unless such hysteria can be curbed many of the advances thathave been made on the behalf of patients with chronic pain can be summarily annihilated.Oxycontin is simply a preparation of an opioid drug that is slowly released over twelvehours to promote even relief without the roller coaster effects and the clock-watchingassociated with short-acting painkillers. The recognition by abusers that this whencrushed, chewed, sniffed or injected, the safety of this miraculous "tiny time pill" couldbe bypassed led major news organs to irresponsibly capitalize on the sensationalistaspects of this criminal misuse of a product that used properly has helped countlesssufferers. This irresponsible journalism has not only disseminated an otherwise obscurestrategy of abuse in the minds of susceptible addicts, but has terrified patients who havebeen benefitting from an otherwise appropriate treatment for years, and has frightenedprescribing physicians and pharmacist who are now reluctant to dispense an otherwisevery helpful drug. Just like a truly resourceful burglar will find a way to circumvent eventhe most stringent security system, an addict who is truly intent on abusing drugs willfind a mechanism to abuse almost anything. The bottom line message is not to throw outthe baby with the bathwater: the answer to curbing addiction to prescription drugs is notto limit their availability, but to teach doctors, patients and pharmacists to communicatemore effectively about a problem that is distressing to all of us.Chapter Four 4 Section Three
  • 103. Patients should be aware that while the risk of addiction is exaggerated by even (wellmeaning) experts, it still exists. Addiction may arise in between 0.1-10% of patients, butit is a treatable disorder, and shouldnt interfere with the consideration of trials of opioidsin patients with lower risk profiles. Individuals who have had difficulties with drugs,alcohol and tobacco in the past are at high risk for addiction and are generally consideredpoor candidates for treatment. Patients in denial who expect a "quick fix" and wish toeliminate rather than manage pain are also likely to encounter difficulties with treatment.Medical Use of Opioids Appears not to Promote Drug DiversionA recent article in the Journal of the American Medical Association (Joranson DE, RyanKM, Gilson AM, Dahl JL: Trends in medical use and abuse of opioid analgesics. JAMA2000 Apr 5;283(13):1710-4) sheds some light on the use versus abuse issue. Theseinvestigators reviewed multiple databases between about 1990-1996. They found that theprescribing of strong opioids increased by 59%, 1168%, 23%, and 19% for morphine,fentanyl, oxycodone and hydromorphone, respectively. Only the medical use ofmeperidine (Demerol fell (by 35%), which is a good thing, since of all the opioids,Demerol is probably the least safe for chronic use because it occasionally producesseizures. Despite this massive increase in prescribing (that has probably increasedexponentially in the last four years), "drug abuse mentions" for these opioids rose by onlydrug (6.6%), and even more impressively, the proportion of mentions for opioid abuserelative to total drug abuse mentions decreased from 5.1% to 3.8%. This article supportsthe view that, like almost anything, opioids are abusable, but that with expert medicalhelp, this is a very rare occurrence, and for years weve probably let a few rotten applesruin things for the whole bushel.Special Prescriptions: A "Chilling" Effect on Doctor, Pharmacist and PatientThe potent opioids are commonly used (like "mothers milk") to treat cancer pain, and wenow understand that they can often be used safely and effectively for chronic pain.Unfortunately, at least in Texas, their use requires a special "triplicate" prescription thatmust be filled within seven days and that cannot be renewed or called in. Also,pharmacies are often reluctant to stock these medications because of extra paperwork andthe fear of robbery, although this situation has improved dramatically in recent years.Most pharmacists now will happily order what patients need if given sufficient notice.Nevertheless, these multiple copy prescriptions have a chilling effect on doctorsprescribing habits, because of the sense that "big brother is watching."Some good news: due to the work of the Texas Pain Society, Dr. C. Stratton Hill, Jr. andother forward-thinking "activists," the situation in Texas is very reasonable. We were thefirst state to pass an "Intractable Pain Act" that states that these medications are, in somecases, indispensable for the treatment of chronic pain and that neither patients nor theirdoctors should be fearful of punishment for their use, as long as that use follows theguidelines of good medical care. There has even been a legislative decision to abolishtriplicate prescriptions in Texas, although it is uncertain how and when this will beaccomplished.Chapter Four 5 Section Three
  • 104. Route of Administration (Pills and Patches preferred to "Shots")One of the biggest hurdles weve had to get over is the lurid media depiction of back alleyinjections and mainlining of drugs, which is a reflection of abuse, not appropriate medicaltreatment. The good news is that we have come to learn that injections are almost nevernecessary. Even the strong medications given by mouth or by a skin patch are just aseffective as injections. Injections are still used around the time of surgery, in emergencyrooms, hospice and when nausea prevents using pills, but almost never for the treatmentof chronic pain. They simply are not needed: chronic pain, however unpleasant anddistressing, is not an emergency, especially when treated proactively.Pain "Contracts"Increasingly, pain clinics are dealing with some of these issues more openly, and oneapproach includes a pain contract. While not necessarily a true legal document, thisapproach simply spells out whats expected of both parties, the patient and the doctor.The "contract" can be implied, verbal or written and often includes expectations like youwill get all of your pain medications from a single doctor, will not "swap" them withothers and will take them only as directed, but on the other hand, that if you hold up yourend, your doctor will take your pain seriously and provide sufficient medications to getfrom visit-to-visit.The Bottom Line: Summing UpWhile opioids are helpful in some cases, they dont reverse the cardinal features ofchronic pain: patients continue to have daily pain with some good and some bad days.These drugs are not a panacea, but simply represent one of the many tools at our disposalto help make this dreadful disorder more tolerable. Moreover, opioids are usually not afirst line treatment, and work best when integrated with other drug treatments likeantidepressants, anti-inflammatories, muscle relaxants and anticonvulsants.Physicians considering trials of opioids for the chronic pain should not view this therapyas a lifelong commitment: discussions with the patient and family members shouldidentify functional treatment goals which will help determine whether treatment issuccessful and should be continued or whether medications should be tapered andstopped. While most patients want pain relief, often at nearly any cost, most experts agreethat a mature and consistent approach to maintaining an active lifestyle is the mostimportant answer for chronic pain. Thus, opioid therapy is best conducted based onwhether patients are able to maintain increases in their functional status. Rather thanrelying on reports of more or less pain which cannot be substantiated, it is optimal to basetreatment on objective outcomes around which the patient, family members and physiciancan agree on. Thus improved mood, nighttime sleep, daytime arousal, socialization,exercise tolerance, range of motion as documented in a regularly kept diary are the mostuseful goals for treatment.Chapter Four 6 Section Three
  • 105. Chapter Four: MHE and Pain Section Four Reflex Sympathetic Dystrophy Syndrome An OverviewContributor: Susan WynnReprinted from The MHE Coalition Newsletter No. 9, March 1, 2002
  • 106. REFLEX SYMPATHETIC DYSTROPHY SYNDROME An Overview by Susan Wynn Reprinted from The MHE Coalition Newsletter No. 9, March 1, 2002Reflex Sympathetic Dystrophy Syndrome ("RSD") is a rare, multi-symptom nervedisorder characterized by chronic, severe pain. It is a disorder of the sympathetic nervoussystem, which regulates involuntary bodily functions such as increasing heart rate,constricting blood vessels and increasing blood pressure. It is a unique disorder, in that itsimultaneously affects nerves, skin, muscle, blood vessels and bones, and it can co-existwith such other conditions as peripheral neuropathies, nerve-entrapment, and carpal ortarsal tunnel syndrome.So why feature information about RSD in a newsletter for patients with MultipleHereditary Exostoses? When my daughter was diagnosed with RSD in 1999, we thoughtthat hers was a rare, isolated case. Nicole suffered tremendously, and it was a difficulttime for our entire family. As her condition improved, we were happy to forget aboutthis experience, and were able to put it behind us until Melanie Barousse posted a plea forhelp on YahooGroups a year ago. The symptoms that she described were so like whatNicole had been through that the memories of that terrible time came flooding back. Icalled Melanie immediately to let her know what Nicole had been through, and that theymight want to present the possibility of RSD to Jakes doctors.Besides Nicole and Jake, there are three other children and one adult in MHEYahooGroups that we know have been diagnosed with this "very rare" condition during a2-1/2 year period. While we are not aware of any studies that indicate MHE patients areat a higher risk for developing RSD, we do believe that at very least, the possibility formore cases exists. Perhaps because of the number of surgeries MHE patients go through,or the nature of the surgeries, or the nature of the disease itself, with compression ofnerves by exostoses being a fairly common occurrence, we feel that people should at leastbe aware of RSD. This article is not meant to alarm, but merely to inform. Because earlytreatment is an important factor in RSD, we are presenting this overview of the causes,symptoms and treatments. If you believe that you or someone in your family may haveRSD, please see your doctor for diagnosis and treatment as soon as possible.What are some of the causes of RSD?While the causes of RSD are not fully understood, it is believed that RSD is associatedwith injury to nerves including:Trauma (even minor injuries, such as a sprain or a fall, can cause RSD); surgery;compression that could cause prolonged pressure on peripheral nerves, such as casting, orswelling due to injury or surgery; heart attack; infection; radiation therapyWhat are the symptoms of RSD?Symptoms and severity may vary from patient to patient and may include the following:Severe, burning pain; muscle spasms; local swelling; softening of the bones; rapid hairand nail growth; restricted or painful mobility; warm, shiny red skin that later becomescool and "bluish"; and pain out of proportion to the severity of the injury. One of themain characteristics of this disorder is that the pain experienced by the patient is moreChapter Four 1 Section Four
  • 107. severe than expected for the type of injury incurred, and that the pain gets worse insteadof better. RSD can begin immediately after the injury, or later. Other symptoms mayinclude increased reflexes, tremors, muscle spasms, fatigue, weakness, skin rashes,frequent infections, and more.What does it feel like to have RSD? We asked the RSD patients in our organization (ortheir parents) to describe the experience: Nicole: "What was it like having RSD? Well, at first I thought it was normal but it hurt a lot. It hurt whenever someone touched it. It felt like acid was dripping through their fingers and onto my leg. When I got home it hurt almost all the time. And when I had to walk with the walker, even though no one was touching it, it hurt even more. It felt like a match was lit and someone put it on my leg. The physical therapy helped make it better, but I left there crying from pain everyday. At home I had to do desensitizing exercises. At first I had to put my foot in a bucket of dry rice. I never knew how sharp and pointy rice could be. It hurt but then we moved on to a bucket full of sand. That was much better and after I was done exercising I made little sandcastles. My foot was blue for a while and still hurt but the pain decreased after a couple of months. Now I am feeling much better." Jake: "After surgery, when we got home the pain started getting worse. It was rrrrrrreally painful! The wind from somebody passing by it and any covering touching it was like somebody taking a pick and stabbing me in that place, but whenever I moved the ankle, it didnt hurt it. When my mom started rubbing lotion on it, even lightly, it felt worse than ever! It felt like an axe instead of a pick and it was bad! Water didnt hurt it, but the washcloth made it hurt like the pick. After a few days of the rubbing and the medicine, it got better. Then the spray really helped. Now it only feels like someone touching it with a spoon. Its not a pain, just a feeling now." Alida: "I am 39 and have had 27 surgeries related to MHE and removing the exostoses. I never had many problems after surgeries until last year. I had about five exostoses removed from my left knee. The nerves were wrapped around the exostoses. It was not right after surgery that all the problems started, but a few weeks later. I was still using the wheelchair. I had gotten the stitches out and went to take a shower. The water hit my knee and I almost fell to the ground, it hurt so bad. It was so bad that I could not stand anything to touch my knee. I was sent for an EMG. I kicked the guy that was poking my leg, and passed out. It was then that they realized how much pain I was in. Even when the sheets touched it, I would almost pass out in pain. I finally got in to see Dr. Patt, a very good pain doctor. He treats mostly patients with cancer, so he knows about pain. He has helped so much with medicine and desensitizing it with rice bags and other things being rubbed on it. I can stand to be touched there now without such pain. It still hurts, and Im just getting used to wearing pants on it. So we are learning more and more about it and it makes it easier to deal with." Robert: "Its a burning, icy, metal pain, and it feels like acid coming out of my foot. It also feels like when you hit your funny bone…"Chapter Four 2 Section Four
  • 108. Brandon: "I had surgery on November 23, 2000. I had surgery because there was a bone in my leg that was making my right foot have a big arch. It also made my foot weaker. Something that happened after the surgery was my leg was very touchy and it hurt sometimes when someone touches it. I never like it being touched because it tickles and feels very odd now. I dont like how it feels. Its like feeling something that is fuzzy, rough, and gentle at the same time. Im supposed to have my mom or dad rub it but I dont like the idea. But it is alright now." Linda: "Johan Olav got RSD after a surgery in September last year. The first day after surgery was "normal" but already the 2nd day I understood something wasnt right. He had severe pain and heavy cramps, his leg was shaking and was "out" of control. We couldnt touch him or the bed, just small things would trigger the "attacks". Ive never seen him in such pain ever before or later, and he has had surgeries both before and after this one. He was really sick for a week or so and then it sort of settled. But the recovery was slow and he still had lots of pain. After 3-4 weeks it took a turn to the worse and he couldnt take it if we touched his leg between the knee and ankle. It seems that soft, gentle touch is worse than firm and things like getting dressed or having something close to the leg is troublesome. His PT worked with him for a couple of weeks, but we could see none or little change. Its more difficult for me to work with it, cause he wont let me. I think hes a bit better now, but he still wakes up if I touch it when hes asleep and he wont let me come near it. Sometimes the pain can just come while hes not doing "anything" and then it looks like he gets cramps and he says it burns."How is RSD Diagnosed?The diagnosis is often made through observation of symptoms and based on a thoroughhistory. Other diagnostic tests that may be used include thermography and nerveconduction studies. Other tests may be used, as required.How is RSD Treated?There are many forms and combinations of treatment. What works for one patient maynot work for another. A variety of drugs, including Neurontin, are used to treat RSD.Corticosteroids, vasodilators, and alpha- or beta-adrenergic-blocking compounds areamong the types of drugs that may be used. Injection of a local anesthetic may also beused, and a prescription spray, Guanethedine, has been shown to be effective in somecases. Other treatments include: Physical therapy, desensitization of the affected area,Transcutaneous Electrical Stimulation (TENS), Nerve Blocks, psychological support, andin some severe cases, sympathectomy may be required to relieve pain. In this surgicalprocedure, cutting the nerve or nerves and interrupting the affected portion of thesympathetic nervous system destroys the pain almost instantly, but it may destroy othersensations as well.Chapter Four 3 Section Four
  • 109. RSD RESOURCESRSDS Association16 Haddon Avenue, Suite DHaddonfield, NJ 08033865-795-8845http://www.rsds.orgRSD Coalition295 Clark Street, Suite 303Worcester, MA 01606508-852-0525http://www.rsdcoalition.comAmerican Pain Foundation201 N. Charles St., Suite 710Baltimore, MD 21201-41111-888-615-PAINhttp://www.painfoundation.orgNational Institute of NeurologicalDisorders and StrokeNIH Neurological InstituteP.O. Box 5801, Bethesda, MD of CAP.O. Box 771San Marcos, CA 92079-0771760-744-3266http://www.rsdsa-ca.orgAmerican Chronic Pain AssociationP.O. Box 850Rocklin, CA 95677916-632-0922http://www.theacpa.orgChapter Four 4 Section Four
  • 110. Chapter Five: MHE and Children Section One The Bumpy Bone Survival GuideContributor: Reprinted from MHE and Me – A Support Group for KidsWith Multiple Hereditary Exostoses and Their Families
  • 111. Nicole Wynn, 14 The Bumpy Bone Club Survival Guide Tools for kids to use with their families, doctors and schools Created and published by: MHE and Me - A Support Group for Kids with Multiple Hereditary Exostoses and Their Families 14 Stony Brook Drive, Pine Island, NY 10969, 845-258-6058,, The MHE Coalition, 8838 Holly Lane, Olmsted Falls, OH 44138 440-235-6325,, Revised October 2005 We are happy to share these tools with other groups. Please credit MHE and Me and The MHE Coalition when adapting the enclosed for use by your group.Chapter Five 1 Section One
  • 112. The Bumpy Bone TrackerAppointment Date:________________________ Time:_______________________Doctor:______________________________________________________________Concerns to Discuss:______________________________________________________________________________________________________________________Examination Notes:____________________________________________________X-rays Taken:________________________________________________________Recommended Treatment:_________________________________________________________________________________________________________________Next Appointment:____________________________________________________To keep track of bumps, it can be helpful to use a color-coded system using tiny stickers or markers, with one color for bumps that you’ve known about, one color for areas that have been operated on, and one color for new bumps that you’ve become aware of since the last examination, bumps that have beencausing pain, or other problems that you’ve noticed. This will help you and your child keep track, and will give the physician an instant overview of things to look for.Chapter Five 2 Section One
  • 113. The Bumpy Bone Pain TrackerThere are many ways to use the Pain Tracker. Using colored markers,draw a line from the picture to a line below and write down all thewords that describe the pain you are feeling in that part of your body.Use a different color for each part that is hurting you. Older childrenand teens may want to simply list the name of each bone and paindescriptions below. Use your creativity and find the way that bestsuits your child. For younger children, please see the following page.For all ages, see the pain diary.________________________________________________________________________________________________________________________________________________________________________ Here are some words that can help describe how it feels when you hurt. Use these or your own words.Aching Bad Spreading SoreThrobbing Pounding Horrible PunishingShooting Pins and Biting LonelyStabbing Needles Cold SickeningSharp Deep Warm PinchingBurning Stinging Miserable LonelyChapter Five 3 Section One
  • 114. Chapter Five 4 Section One
  • 115. The Bumpy Bone Pain Tracker For Little Kids! HOW DO YOU FEEL?Put a mark on the line that shows how you feel. If you don’t have any pain, put a mark near the happy face. If you’re hurting, put a mark near the sad face. If you hurt a little, put a mark in the middle. Where Does it Hurt? Illustrated by Nicole Wynn, 14 Let your child color in each of the squares below in a different color. Explaining what each color means, let him or her then color in the drawings to show how each part of the body feels.Chapter Five 5 Section One
  • 116. Pain DiaryThis diary can be kept by parents and/or child. Make additional copiesas needed, or print from the MHE and Me website www.mheandme.comWhere was the pain? (You can attach a copy of the Pain Tracker andshow where the pain is on the picture, or describe the location here).______________________________________________________________________________________________________________When did the pain start? ___________________________________Activity when the pain started (Sleeping, running, walking, sitting,climbing stairs, playing a sport, etc.):________________________________________________________________________________How bad was the pain on a scale of 1 to 5, with 5 being the worst?___Describe the pain (You might want to see if some of the words listedon the Pain Tracker describe your pain)_________________________________________________________________________________Was any treatment tried? (Medication, heat, ice, rest, etc) Describe:________________________________________________________________________________________________________________Did it help?_______________________________________________How long did the pain last? __________________________________For young children, what was the child’s behavior like duringthis episode of pain (crying, withdrawn, cranky, etc.): ___________________________________________________________________Additional comments or notes:________________________________________________________________________________________Chapter Five 6 Section One
  • 117. Chapter Five: MHE and Children Section Two The MHE and Me Handbook A Guide for Family, Friends, Teachers and ClassmatesContributor: Reprinted from MHE and Me – A Support Group for KidsWith Multiple Hereditary Exostoses and Their Families
  • 118. THE MHE and Me Handbook A Guide for Family, Friends, Teachers, and ClassmatesDISCLAIMER: While many find the information and experiences that we share helpful, it isin no way a substitute for professional medical care. Our support network does not engage inthe practice of medicine. In all cases, we recommend that you consult your own physicianregarding any course of treatment or medicine.WHAT IS MHE?Multiple Hereditary Exostoses (MHE) is an inherited disorder of bone growth. Peoplewho have MHE grow exostoses or bony bumps on their bones that can vary in size,location and number depending on the individual. Although any bone can be affected, thelong bones: legs, arms, fingers, toes, ribs; pelvis and shoulder blades are the mostcommon. MHE can be referred to by various names such as Heredity Multiple Exostoses,Hereditary Multiple Osteochondromata, Multiple Cartilaginous Exostoses, etc.An exostosis is a benign bone growth that is abnormal or different than the underlyingarchitecture of the bone. These bone growths generally grow out or at an angle from thenormal bone. Sometimes doctors refer to exostoses as "tumors" which like "exostoses" isa general term meaning abnormal growth. It is important to remember that not all tumorsare cancer. Most tumors like the exostoses of MHE are benign. Exostoses grow near thegrowth centers of the bones which are near the ends of the bones. That is why manybumps grow near joints. Exostoses can be rounded or sharp and will continue to growwhile a child is growing.This condition is not contagious. MHE is a condition that is passed by the genes of theaffected parents to their children. It is called an "autosomal dominant" disorder whichmeans that if one parent has the condition, chances are fifty percent that their child couldalso develop MHE. Occasionally, a person can develop multiple exostoses with no familyhistory of MHE. This situation is described as a spontaneous mutation meaning a geneticproblem arose in that person without being inherited from a parent.HOW ARE CHILDREN AFFECTED BY MHE?Some children will have few if any symptoms while others are severely affected and willhave a great deal of difficulty. Because the bone growths can cluster around joints,children with MHE can have a great deal of difficulty with normal movements such aswalking, running, lifting, carrying, bending joints, kneeling, grasping and arm and legrotation.Tumors can grow and increase at any time, but particularly during growth spurts. A childwho has no problem with a movement one day may find that movement restricted thenext and then back to not being a problem the day after that. A tumor may also grow insuch a way as to create an entirely new restriction on a childs mobility. For example, achild who was able to sit in a certain position during the last semester may not be able tosit in that same position this semester, or in the future. A child who could run may not beable to do so following tumor growth. Some mobility problems may be corrected bysurgery, but some may become lifelong limitations. Parents as well as teachers workingwith children with MHE must be aware of the changing nature of this disorder.Chapter Five 1 Section Two
  • 119. While children with MHE may seem extremely fidgety, they may be simply trying to getcomfortable. Many tumors cannot be seen and their affects can be subtle. One child withMHE may have multiple tumors at many different sites in the body, while another childmay have only one or two tumors. No one yet understands why different people areaffected differently at different parts of their body.HandsHand and arm problems can present unique challenges. MHE children may haveproblems manipulating small objects. For the younger child this may mean difficultybuttoning, zipping, and tying; skills which children need to dress themselves. Olderchildren and adults with MHE can also have trouble with these skills. An MHE child inpreschool or kindergarten may need help with these tasks, leading observers to feel thatthe child has not yet met developmental guidelines for self care. Caregivers need tounderstand what the child is physically capable of and help them compensate. Forchildren who cannot get their fingers to work correctly to tie shoes, velcro has been foundto be a wonderful adjunct that helps MHE kids with independence. Most MHE kids learnto compensate and do things in their own unique way while still accomplishing the goalsof independence.For the older child entering primary school the challenges can be daunting. Holding apen, pencil or crayon may cause discomfort and pain. "Nicole (10) has many, many bumps on her fingers and they get stiff and hurt where the pencil or pen rubs against them. We recently found foam rubber pencil grips that cushion. We also found special pens and automatic pencils that are large and cushioned. These do help but when she has a lot of homework her hands hurt and she becomes quite fatigued."Even when a child can hold a pencil and appears to be doing fine other problems canarise: "Julianne (age 10) has trouble with pain in her wrist and the teachers just dont understand. They keep giving her more handwriting homework as if she just needs to practice more. She uses little cushions and thumb pillows; that is all we were able to change. She just will not be able to get an "A" in handwriting. But she tries hard and that is what counts!"But even with cushions and special pens and pencils these children have severe problemswriting for long periods of time. "Bobby (8) has trouble gripping a pencil. He is in third grade and there has been a huge increase in writing. After much discussion with school staff, the school district has provided him with an Alpha Smart Keyboard. It is quite small, displays several lines of text and has a memory. He takes it everywhere with him and can complete writing assignments on it that can be printed out either at home or in the classroom."For other children the problem may be more subtle: "Christopher (13) cannot grip a pen or pencil properly and his handwriting is atrocious. His teachers constantly complain that they cannot read his writing."Chapter Five 2 Section Two
  • 120. Needless to say, these kind of problems can lead to difficulties handling and manipulatingother common objects in the school environment: scissors, chalk, glue sticks, paper clips,rubber bands, and the myriad of other small manipulatives that young children use in theclassroom.ArmsThere are two bones in the forearm, the ulna and the radius. The radius extends from thewrist on the thumb side of the arm while the ulna is on the little finger side of the arm. Inmany kids with MHE the growth of the ulna is affected and it is quite shorter than theradius. This can cause the radius to "bow", pushing the hand to "cock" at an angle. Thiscan cause severe wrist problems. Some kids with MHE cannot supinate or pronate theirhand because of lack of rotation in the wrist. They will compensate by turning theirwhole arm from the shoulder, bending their elbow into the body to achieve supinationand moving the whole arm in the other direction to achieve pronation. In the classroom,the child may be asked to do things they simply cant. For instance, at circle time when allthe children join hands, the child with MHE may not be able to comfortably turn his handto hold the hand of the child next to him. The child and his parents may not even havebeen aware of this problem with mobility.Exostoses around the shoulders can prevent the child with MHE from rotating theirshoulders: throwing a ball, playing windmills, playing airplane. An exostoses can affect,limit, or even totally block movement. Also, straps from backpacks can rub againstexostoses causing discomfort and pain. Trying to hold heavy books can also be a problemfor the MHE child. It may be necessary for a child to be provided an extra set of books athome so that the daily burden wont be too great. Kate (26) "I could never swim freestyle/overarm; only breaststroke. In Australia, you learn to swim at primary school. My shoulder wouldnt ever rotate enough to swim overarm even after surgery. I cant swim very well because my arms are very different lengths and have very different strengths and I swim in circles."Ankles and FeetThe foot has many, many bones and most of these are considered "long" bones andsubject to the development of exostoses. When an exostosis forms and grows it can affectthe length of the bone, shortening it considerably. Children with MHE can have prettystrange looking feet: bumpy, lumpy feet with minimal or even nonexistent toe nails. Likethe fingers, toes can be longer or shorter than normal even on one foot. The big toe can belonger than usual while the toe right next to it can be shorter than normal. Ellen (16) ";I have really strange feet - toes completely out of order, and they make footprints with three toes only. So that was thought of as strange but in an "arent-you-lucky" kind of way."Pain and discomfort walking, as well as an uneven gait may be caused by valgusdeformity. This condition is caused by bone growths around the tibia or fibula, whichcause the ankle to bend outward. Melissa (15} "One of the things that bothers me a lot is my ankles. I cannot stand it if anything touches them, like shoes or heavy socks, or even when I go to sleep. It bothers me when I lay down and they touch the bed."Chapter Five 3 Section Two
  • 121. MHE kids may be unable to stand on tiptoe. Bone growths in the metatarsals can push thetoes to the side causing the big toe and the other toes to form an angle pointing to theoutside of the foot called hallux deformity. Hallux is the great toe.LegsUneven growth caused by exostoses can cause the fibula or tibia to be shorter. This cancause the other bone to bow out. To even out the bones growth an external fixator can besurgically attached, which over a period of months causes the bone to lengthen. Somechildren may be candidates for this surgery, while other children may qualify for aprocedure wherein staples are surgically inserted into the growth plate at the end of thelonger bone to slow its growth and give the shorter bone a chance to "catch up" Lydia (17) "My legs give me the most trouble and sometimes it feels like there is constant pain, the sort of pain that I can live with or I just got so used to it. I think they hurt more when I sit all day. A little walking actually helps and it feels like I can "walk" away some of the pain."Surgery that is meant to offer a solution to a problem can have its own complications: "Nicole (10) had surgery over summer vacation: stapling of the proximal tibia (near the knee) and removal of a large exostosis just below that. Three months later she had to have surgery on the same leg to remove three exostoses from the fibula which were compressing a nerve and had caused a nerve palsy resulting in drop foot. Drop foot is the inability to move the foot. Nicole is being tutored at home while she recovers and undergoes extensive physical therapy to relearn how to walk."KneesBone growths around the knees can cause limited flexibility or even inability to bend theknee and can cause the child to be unable to kneel because of pain. Bone growthsfrequently make the knees appear bulky and larger then normal. Many kids with MHEcannot sit on the floor cross-legged not only because of bone growths around the kneesbut also bone growths around the hips and pelvis. Gil (53) "I cant get into a crouch, you know like catchers do. I have never been able to crouch. My knees only bend about 40 degrees. My knees used to give me a lot of pain when I was a kid but once I got older they only hurt occasionally."Hips and PelvisAs mentioned above, growths around the hips and pelvis can make it impossible for achild to sit cross-legged on the floor but these can also cause other mobility problems. "Susie (age 11) has trouble with stairs. She cannot get her leg into the proper position to climb to he next step. She must take each stair one step at a time. She steps up with her right leg and then brings the left one up. Her left leg is more severely affected due to tumors on her hip and pelvis. She also has a bone growth above her knee and in the back of her leg that prohibits her bending that leg very much. She climbs the stairs at an angle."Hip and pelvic tumors can prevent a child from bending over, touching their toes orspreading their legs.Chapter Five 4 Section Two
  • 122. RibsExostoses can form on the inside of ribs or the outside. Roger (21) "They can catch on the muscles in your chest, which can make it really painful to even breathe. It is possible to uncatch them - to basically shove your chest muscles back to the other side of the offending lump and this takes away the pain."Skull, Neck and SpineAlthough bone growths of the skull, spine and neck are extremely rare they can occur.THE MHE CHILD IN SCHOOLBecause the affects of MHE can be so varied from child to child it is important to keepthe school apprised of any changes. Before the child is enrolled in school, write theschool and let them know that your child has a disability and what mobility limitations orpain problems your child may be having. If you notice a new limitation, write the schooland let staff and teachers know exactly what it is and what affect it may have on yourchilds participation. If the situation over the summer break changes, for instance asurgery or new limitation is noted, write the school and let them know. At the beginningof every new school year, a letter explaining MHE directed to staff and teachers wouldhelp refresh the schools memory that your child has special needs.THE MHE CHILD AND PE CLASSThis is an extremely difficult area because MHE children can be affected in so manyvarious ways and in so many different body parts. On top of this, children with MHE maybe able to do a certain motion one day and find that same motion constricted or painfulthe next. Most MHE children can participate in physical education but the instructor isgoing to have to be not only aware that the child has special needs but also sensitive tothe changing status of the MHE child. A child who says they cannot do a particularmotion or function should be respected. If there is any doubt about the veracity of suchstatements, parents or guardians can be contacted for verification. Children with MHEshould not be encouraged to "just try" something they have said they cannot do. SomeMHE kids appear "normal", while other children will have obvious deformities.Some children with MHE may reach the point where they are unable to participate inphysical education classes for extended periods of time; some may not be able toparticipate at all. This may be due to the need for surgery to relieve an obstruction orsimply because the movements necessary for physical education class are impossible orcause too much pain. Even after surgery to relieve an obstruction caused by a bonegrowth, the child may never be capable of full mobility. All children want to "fit in" andbe treated the same as the other kids. Children unable to participate in sports should notbe looked down upon or made fun of. They should also be encouraged to use that classtime for a productive activity, such as library time, etc. Many children with MHE havephysical therapy exercises they can do during this time.Chapter Five 5 Section Two
  • 123. FATIGUEMHE kids can tire easily. Exostoses can put significant pressure on vital structures,making it necessary for the child to stop all physical activity for periods of time. A childmay be dealing with a lot of mobility issues and be in pain. Pain in and of itself can beexhausting. Some MHE kids and adults note a significant increase in pain during wet andcold seasons. In addition, many children suffer from night pain and discomfort severeenough to interfere with their sleep. The performance of these children in school the nextday will obviously be affected by their lack of sleep and their physical discomfort. Whenfatigue becomes a major problem, a child with MHE may have to go to half days or havea tutor come to the home to continue schooling. "Andrea (8) suffers from over-all fatigue. By the end of her school day I have to meet her at the bus and carry her backpack, and she holds on to my arm to help "pull" her up the road to our house. She takes breaks when she needs them but sometimes other kids, including her sister, just cant understand that she cant keep up with them and has to rest."DISABILITYSection 504 of the Americans with Disabilities Act is not an education law but a civilrights law that prohibits discrimination on the basis of a disability. The intent is to meetthe needs of disabled students in the least restrictive environment possible. Section 504finds a person as having a disability if the person:1. Has a physical or mental impairment which substantially limits a major lifeactivity;2. Has had a physical or mental impairment which substantially limits a major lifeactivity, or3. Has had a physical or mental impairment which substantially limits a major life activity, or is regarded as having a disability by others.Section 504 requires the provision of a free and appropriate public education (FAPE).School districts that receive federal funds are required to establish procedures for theevaluation and placement of students with disabilities who require either specialeducation or related services.Major life activities include walking, seeing, hearing, speaking, breathing, learning,working, caring for oneself and performing manual tasks. The disability need onlysubstantially limit one major activity in order for the student to be eligible.MHE AND PAIN MANAGEMENTSimple AnalgesicsIn MHE there are primarily two different kinds of pain: the sharp pain of having a bonegrowth bumped, hit, or knocked and an achy pain and discomfort that can be mild orsevere and that can last for minutes, hours, days or weeks. Any pain that is not relievedwith pain medications, impinges movement, or recurs should be checked by a doctor.Dosages of various pain medications can be tailored to the needs of the patient, butyour doctor should again determine this. Acetaminophen has the potential to be toxicbut larger doses than is normally recommended can be prescribed by your doctor tohelp with pain management. Always consult with your doctor before changing dosages,combining medications or starting a new pain medication.Chapter Five 6 Section Two
  • 124. Normal recommended dosages of pain medications like Acetaminophen (Tylenol) andIbuprofen (Motrin, Advil, etc.) can be very helpful in pain management but can lose theireffectiveness over long periods. Your physician can prescribe stronger dosages to helprecalcitrant pain. Never increase the dose of a pain medication unless under the adviceof your doctor. Acetaminophen can be dangerous and toxic in too large a dose. Aspirinis never recommended in children. MHE can cause long term, recurring pain. Some havefound a dose of pain medication used as a prophylactic at night can help with sleepproblems due to pain. This is a very individual decision as the use of long term painmedications have complicated implications and any use of long term pain medicationshould be under the supervision of your doctor.Heat Providing DevicesFor simple episodic pain many have found heat to be an immense relief. Electric heatingpads, hot water bottles, gel packs and fabric bags with organic husks can all be useful.Heating pads can be dangerous for those who get pain in the night and fall asleep. Thereis the danger that the heating pad can overheat and burn if it is left on unattended, kinkedor rolled over on. Hot water bottles are old fashioned but much safer. They do not gethotter but gradually cool down. Gel Packs and husk bags can be quickly heated in themicrowave and also gradually cool down. Organic husk bags come in many shapes andsizes and many can be wrapped around the painful area providing great ease and comfort.Uncooked rice can be sewn into a fabric bag of any desired shape or size and warmed inthe oven or microwave. It can then be placed on or wrapped around the painful area. Fora child with pain in the night these are much safer alternatives then a heating pad and canhelp to speed everyone back to sleep. Night pain is common in children with MHEbecause the distraction of daytime and daytime activities can mask pain until the childcalms and tries to sleep; then they feel the pain.Pads and cushions on chairs can help relieve discomfort sitting and a feather bed cancushion bumpy bones that are difficult to sleep on.During the day at home, warm baths, hot tubs, warm showers can ease mild pains.Pain at SchoolThe use of pain medication at school can become complicated and controversial. Again,some parents opt for the use of a pain medication as a prophylactic to try to prevent painwhile the child is in school. Many parents feel this much use of pain medication is notwarranted and can be dangerous. Children with MHE can have a private place at schoolwhere they can rest, take pain medication if warranted, use a source of warmth to easepain and then return to class when they feel better. Many school districts insist that painmedication be kept in the office under the supervision of a nurse or secretary. This is notalways feasible. A parent reports: "I asked that my third grade son have his pain medication available in the classroom to be administered on an as needed basis for pain by his teacher. I was told no, that medications had to be in the office. Well, one day when my son asked to go to the office to get pain medication the teacher told him to wait until the spelling test was over. By the time he was allowed to go to the office, the pain had escalated. The classroom was in a bungalow and he had to cross the playground to get to the office. He didnt make it. Something called me to his school that day and I found him lying in the rain against a wall in too much pain to walk. He was soaking wet and crying; not only in severe pain but extremelyChapter Five 7 Section Two
  • 125. frightened. I really dont know what would have happened if I had not listened to my instincts and gone to check on him that day. Since then I have absolutely insisted that his pain medication be available to him in his classroom. Sometimes it has been quite a fight but when I tell them this story they understand and make an exception."Sometimes, simply asking the school to make accommodations works. Schools seemmuch better prepared for scheduled doses of medication like antibiotics. The "as needed"basis of pain medication can make school staff very nervous; and rightly so. If the childhas pain in the morning and the parent medicates and three hours later the child has morepain it is not appropriate for more medication. A simple form can be designed that travelswith the child and contains dosing information. That way neither school staff nor parentshave to worry that the child is being "double dosed."Younger children present some unique problems. When my son was in kindergarten, his teacher noticed a pattern of behavior and expressed her concern to me. My son would get very quiet and withdrawn and then would act out by being mean and sometimes actually hitting other children. This was quite contrary to his normal behavior. We were able to identify this as pain onset. He would not tell the teacher he was in pain because he did not want to stand out and be different so he would ignore the pain until it was quite bad. The teacher learned to recognize this behavior and would take him aside, ask if he was in pain and quietly and privately give him pain medication and a quiet place to rest until the medication took effect. Eventually, he was at ease and was able to simply go and ask her for his pain medicine."Young children in pain can be angry and aggressive or can regress and mimic youngerchildrens comfort behaviors: thumb sucking, rocking and other self-comfortingstrategies. A perceptive, sympathetic teacher can intervene, minimizing disruption andstress in the classroom.Non-traditional Pain AlleviationPrimarily in this category would be acupuncture, acupressure and chiropractic. Manytraditional doctors have become knowledgeable about these alternative modalities.Results have been very mixed with some reporting a great benefit and others reportinglittle or no benefit.Stress can aggravate pain. A child in a classroom where everyone knows and understandshis medical condition may experience less stress and therefore a reduction in pain.New ResearchIn the past few years, pain management has become its own subspecialty in medicine andthere is more of an emphasis on research and the development of new pain medications.In the past, intractable pain was unfortunate but not much could be done to alleviate itwithout the use of narcotics. New philosophies regarding pain management and newmedications for pain are being developed all the time. Celebrex has been shown to be aneffective pain alleviator but is not appropriate for young children and can have distressingside affects. Another new improvement in pain management is the recent discovery thatlow doses of antidepressants can alleviate pain. Again, your own doctor is your bestsource of information on new developments in pain management.Chapter Five 8 Section Two
  • 126. There are many options available and working closely with your doctor is critical inalleviating serious or chronic pain. At different ages, at various times, and even duringdifferent seasons of the year, different strategies can be used, combined or discontinued.When one thing stops working move on to try another; you can even go back to trysomething that worked in the past. Pain can be managed and alleviated. There is noreason for children to suffer unnecessarily.ORTHOTICSMost children with MHE will need some form of medical treatment at some time. Somechildren with MHE will need orthotics: braces, splints, supports, casts, walkers, crutches.Not only can this type of equipment limit mobility but also it can be embarrassing to achild who wants nothing more then to not appear different. "My son had to wear a cast on his left foot and ankle and had to wear a brace on his left wrist. He was constantly questioned as to why he had to wear these but he was also teased by classmates that he had been in a car accident and only been hit on his left side. After a couple of days of teasing he did not want to wear the brace (although he needed it) and insisted that the cast be removed early (it couldnt be)."The teacher could simply explain to the class, with the child and parents permission, thatthe child has a bone condition and that this type of equipment helps the child function.Once children understand the function of an orthotic they tend to move beyondfascination and confusion to simple acceptance.SURGERYOften the treatment will also be surgical and the child will be hospitalized. Some childrenwith MHE will have numerous surgeries. Surgery is usually an extremely traumatic eventfor a child or even for an adult. Children may experience anxiety once they know thatsurgery will be scheduled. They may require pre-surgical tests that are frightening and/orpainful, and they naturally fear the operation, pain, discomfort and scarring they willexperience afterwards. They may miss a significant amount of school and will needhelping catching up. Returning to school while still in some degree of pain, weakness andawkwardness can be quite challenging. Many children with MHE have to wait to havesurgery until growth plates fuse (at fifteen or sixteen). If surgery is performed too soon,the exostoses can simply grow back.Consideration needs to be given to children in these situations. Understanding theirneeds, abilities and limitations must be looked at realistically to make it a smoothtransition for all concerned. By law, schools are required to take responsibility for someof these needs. It is important for all concerned to discuss and plan a childs return toschool after surgery and to realistically schedule make up work. Again, a simpleexplanation to teachers and classmates of what the child has been through and why willhelp alleviate anxiety for everyone. Before and after surgery, the child can be providedwith a tutor to help stay as current as possible with schoolwork and to help the transitionback to the classroom when it is deemed appropriate. The provision of a tutor issomething your school district should provide. "In my school district they have a program called Home/Hospital for kids who have a serious illness, injury or surgery. The tutor comes to our home once a day for an hour and she has truly been a godsend. She talks to his teachers at school and picks up assignments and supervises his completing them. Every time he hasChapter Five 9 Section Two
  • 127. had to miss school for long periods because of pain or surgeries we have had the same tutor. It has really helped my son keep up in school."EMOTIONAL ISSUESSelf EsteemChildren with MHE may grow up thinking they are the only children in the world whohave this disorder. They may become very self-conscious about the appearance of theirbumpy bones, bowed or shorter-than-average limbs, their inability to walk or run orperform other sports related activities in the same manner as their peers. As childrengrow older, they become more and more aware that they are somehow different. Somechildren may stop wearing shorts or short sleeved shirts, in an attempt to hide thephysical signs of MHE.Most of us are more comfortable with what we understand. Many parents have reportedthat a short teaching component on MHE piggybacked with another study area, forexample, the skeleton helps everyone understand MHE and feel more comfortable,including the child who has MHE. "My daughter would never allow anyone to know she had MHE. She was too afraid of being different and of being made fun of. By the time she reached the fourth grade her symptoms became too severe to ignore and the school personnel had to be notified. She required individual counseling by the school psychologist to deal with her feelings of insecurity and low self-esteem, and to deal with anxieties over her first surgery, which would take place during summer vacation. As she needed more and more "special" treatment (she had to sit on a chair instead of the floor, and be excused from many activities in gym) her classmates needed to be told about MHE. She was amazed that no one made fun of her. In fact some of her friends were jealous that she got to sit on a chair during assemblies, while they had to sit on the floor! A weight was lifted from her shoulders when she stopped feeling that she had to keep her disorder a secret." "I once asked my son what bothered him most about his bumpy bones and he said, Nobody else has them."Some children can become angry or depressed: "I am just 10 years old and I have lots of trouble with my bones in school. I hurt a lot when I write new teacher is real tough and I dont think she is going to understand my not being able to write very much. Being 10 isnt easy, but it really isnt easy being 10 and have crummy bones and being small."Teasing and OstrasizingChildren with MHE can appear "different". Part of the curriculum of every school shouldbe the appreciation for and respect of others and our diversity. The terrifying increase inviolence in our schools should teach us one basic lesson: we all need to learn to respecteach other and treat each other with courtesy. Mike (13) "A kid walked up to me on the playground and looked at my arms which are visibly deformed. He stared and then started chanting, "What are you some kind of mutant?" He said this several times and then asked, "What are you retarded, too?" when I didnt know how to answer him."Chapter Five 10 Section Two
  • 128. A simple teaching component on MHE would probably have alleviated this childsconfusion and lessened the chance of his saying something so obviously inappropriate.We tend to fear what we dont understand.AchievementThe most important step in making life easier for a child with MHE is also the hardest,and that is recognizing the childs difficulties. Children need to feel loved and valued justas they are, whether short or tall, thin or heavy, lumpy-boned or perfectly formed. Onceparents, teachers, and others come to terms with the childs limitations, they can talkabout them with the child in an open and realistic way. Children may have a hard timeputting their feelings into words, but that does not mean they dont have feelings aboutbeing different. Children with MHE usually know they are different by the time theyreach school age, if not before. These children may be relieved to have parents, teachers,and friends who can help them identify and express feelings about being different.In a society that values achievement and being the best, be it in sports, school, orbusiness, it can be difficult for some to understand that not all limitations can be"overcome". For many children with MHE the simple act of finally being able to tie ashoe can be a major milestone. That accomplishment, however, does not mean that childis now capable of running a race. Too often we set unreasonable expectations for ourchildren, whether able-bodied or disabled. The media shows us examples of amputeesskiing and paraplegics playing basketball. While these are laudable achievements, theyare not realistic goals for every disabled child, just as not every able-bodied child willbecome a professional ball player or figure skater or Olympic Gold Medal winner. "My daughter has shown amazing courage and strength in relearning to walk after several tumors in her leg stretched and entrapped a major nerve there. However, sometimes people think that recovery from an MHE surgery is just like recovering from a broken leg. They think you heal and are done with it. They dont realize that there can be other tumors in other places that are still blocking and restricting other movements, causing other problems. Sometimes someone will make a comment on how my daughter will be able to do this or that soon, and shell reply that she wont be able to do that. People think theyre helping by saying things like, "My family motto is never say never!" My daughter knows her body and she knows her limitations, but she also knows her talents and her strengths, and that should be enough! Sometimes you have to acknowledge that "never" is the reality, accept it, and move on to what is possible!"MHE AND TEENS:As children with MHE enter their teen years the challenges of living with this disordermay intensify. Many surgeries for MHE take place after the growth plates close whenchildren are fifteen or sixteen years old. Add that to the normal challenges of being ateenager! "As a 17-year-old girl, I find it very hard to be different from other people. Im strong enough to be my own person mentally, but its tough to be physically different. My fingers are short and the way my fingers grew on my left hand it looks as though what should be the third and fourth fingers were switched! , Im shorter than I should be. What has been the worst is what this disease has done to my ego and self-confidence. In the beginning of high school you learn that being different is not all right, and therefore not attractive. "Chapter Five 11 Section Two
  • 129. But even when the teenager feels they are dealing well with the implications of theirdisease the people around them can still have a profound effect: "Today in my psychology class we were all asked to introduce ourselves and discuss a hardship that we had to face in our lives. Stories ranged from the death of a parent or friend, parents divorces, to being grounded or getting a speeding ticket. Obviously, my toughest hardship to date has been MHE. So, when it was my turn I stood up and told the class that I have a bone condition where spurs form on my bones, usually at the growth plates, and because of that Im short, have abnormally short fingers, and have eight scars on my knees and right wrist. That I was unable to do anything very athletic or lift heavy objects, walk up the stairs from the first floor to the fourth. The teacher was nice, she asked questions about malignancy, if I knew other people with the condition, and how it might affect me later in life. The stares; I hate the stares the most. High school students know nothing about compassion. I either was getting looks of extreme pity, or scared looks, almost as though half of the class was afraid they would get it just from being in the same room with me. It isn t the common cold, you know! Seems to me the looks of pity should go towards the poor people who have lost a parent or good friend, not to the girl with the bone condition and the scars. Its so frustrating a lot of the time. I deal with my bones well and without much self-pity. Why cant other people?" This Handbook has been designed to help educate those who have MHE, but more importantly those around children with MHE: parents, family members, teachers, classmates and friends.We would like to offer a special thank you to the many families affected by MHE whograciously shared their experiences and insights with us.Without their help, this Handbook would not have been possible. MHE and Me A Support Group for Kids with Multiple Hereditary Exostoses and Their Families 14 Stony Brook Drive Pine Island, NY 10969 845-258-6058 MHE and Me is a proud member of The MHE Coalition Last Update: October 4, 2003Chapter Five 12 Section Two
  • 130. Chapter Five: MHE and Children Section Three Common School Concerns for Students with MHE School Needs Checklist for Kids with MHEContributor: Reprinted from MHE and Me – A Support Group for KidsWith Multiple Hereditary Exostoses and Their Families
  • 131. Common School Concerns for Students with MHEHaving Multiple Hereditary Exostoses does not affect a childs ability to think and learn.However, pain, fatigue, and mobility issues can affect both a childs ability to concentrate and achilds performance in school. The following are just a few of the many challenges that might bepresent for a child with MHE, as well as some possible solutions. It is important to develop apartnership with your childs school to find the best solutions for your childs particular needs.Some schools will supply needed accommodations on an informal basis; other times it will benecessary, and often desirable, to obtain a 504 Accommodation Plan or Individual EducationPlan (“IEP") for your child.It is important to remember that some of the most valuable ways to help your child arecommunicating with your childs teacher(s) on a regular basis, and informing school personnelwhen there is any change in your childs condition. There may be times when modifications arerequired due to fatigue and decreased endurance levels, new problems with pain and/or mobilitydue to exostoses growth, scheduled surgery and recuperation, etc. Unless you let the schoolknow what is happening, they will not understand what your child is going through.Accommodations are not something that are just given. They must be requested and justified,and it is often up to the family to make appropriate suggestions as to what will best help theirchild.Remember that you are your childs best advocate, and that it will be necessary for you to teachyour childs educational team (teacher(s), school nurse, administrators) about MHE and how itaffects your childs educational needs. To learn more about your childs educational rights,contact The National Information Center for Children and Youth with Disabilities (NICHCY),P.O. Box 1492, Washington, DC 20012, 1-800-695-0285, http://www.nichcy.orgDifficulty:Difficulty climbing stairs or walking long distancesStrategies:*Request elevator permit*Schedule classes to decrease walking and climbing*Request extra time getting from class to class*Use a wheelchair if neededDifficulty:Inactivity, stiffness due to prolonged sittingStrategies:*Change position every 20 minutes*Sit at the side/back of room to allow walking around without disturbing the class*Ask to be assigned jobs that permit walking (collect papers, etc.)Difficulty:Difficulty carrying books/cafeteria trayStrategies:*Keep two sets of books; one in appropriate class, one at homeChapter Five 1 Section Three
  • 132. *Have a buddy to help carry books*Determine cafeteria assistance plan (helper, reserved seat, wheeled cart)Difficulty:Difficulty getting up from deskStrategies:Request an easel top desk and/or a special chairDifficulty:Handwriting difficulty (slow, messy, painful)Strategies:*Use "fat" pen/pencil, crayons, special pencil grips*Use a felt-tip pen*Stretch hands every 10 minutes*Use a tape recorder for note taking*Photocopy classmates notes*Use a computer for taking notes, reports, etc. Many students with MHE have had good resultswith the AlphaSmart Keyboard*Request an alternative to timed tests (oral test, extra time, computer)*Educate teacher - messy handwriting may be unavoidable at timesDifficulty:Difficulty with shoulder movement/dressingStrategies:*Wear loose-fitting clothing*Wear clothes with Velcro closures*Get adaptive equipment from occupational therapistDifficulty:Difficulty reaching lockerStrategies:*Modify locker or request alternative storage place*Use two lockers with keylocks instead of dialsDifficulty:Difficulty raising handStrategies:Devise alternative signaling method This material has been adapted for children with MHE (c) 1998, Raising a Child with Arthritis. Used by permission of the Arthritis Foundation, 1330 W. Peachtree Street, Atlanta, GA 30309. For more information, please call the Arthritis Foundations Information Line at 1.800.283.7800 or log on to MHE and Me - A Support Group for Kids With Multiple Hereditary Exostoses and Their Families 14 Stony Brook Drive, Pine Island, NY 10969 mheandme@yahoo.comChapter Five 2 Section Three
  • 133. School Needs Checklist for Kids with MHEYou and your child can work together on this checklist or, depending on his or her age, our childmay be able to answer questions alone. It can give your childs teacher a good idea of your childsstrengths and weaknesses. A = always, S = sometimes, N = never, NA - does not apply to meGetting Ready for School___ I can get out of bed without any help and withoutholding on to anything.___It takes me less than 30 minutes to feel good after ___I find it hard to hold my pen or pencil.I get up in the morning. ___I find it hard to write on the chalkboard.___I must take a bath or shower to loosen up in the ___I find it hard to use scissors to cut.morning. ___It is hard to raise my hand in class because of my___I can go up and down the stairs when I first get MHEout of bed ___I find coloring difficult.___I can fully dress myself and put my shoes and ___I find painting difficult.socks on quickly in the morning. ___I get so tired at school, I want to rest.___I can tie my shoes. ___Im afraid some of the other kids will knock me___I have a lot of pain in the morning before I go to ___I get frustrated because I cant always keep up___I need to bring splints, crutches, a walker, cane, with the other kids.or wheelchair to school to help me during the day. ___I find it difficult relating to the other kids at___I go to school later in the day than the other kids schoolbecause of my MHE. ___I would like the other kids in my classroom to___I take pain medication before I go to school. know I have MHE as long as they dont treat me differently.Getting to School ___I find it difficult putting on or taking off my gym___I can walk to school or the school bus stop clothes.without any difficulty or help. ___I find it hard participating in regular gym___Waiting for the school bus is easy. activities.___I can get into the school bus without any ___Playing outside in cold is difficult for me.difficulty.___I need my parents to drive me to school or I take I Find It Difficult To:special transportation provided by the school. ___ run ___jump ___hop ___skip ___bend ___climb ___pull ___hang ___ push ___pullActivities at School ___kick ___throw ___tumble ___wrestle___I can go up and down stairs quickly at school ___play soccer ___play basketballwithout any difficulty. ___play volleyball ___play contact sports___I can use the elevator at school by myself without ___other _________________________________any difficulty.___I need to get up and walk around in the classroom After School Activitiesbecause of stiffness or pain. ___I need to take a nap or rest period when I get___I can carry my own lunch tray. home from school.___I can open my own milk carton ___I can finish all my homework every night without___I need to take pain medication at school difficulty___I get embarrassed when I have to go to the school ___I can participate in after-school activities withoutnurse. difficulty.___I can use the bathroom by myself at school ___I cannot get through the school day and must gowithout any difficulty. home early.___I find it easy to carry my own books at school andto and from school. MHE and Me___I can write at school without any pain or stiffness. A Support Group for Kids___I find it difficult to write quickly. With Multiple Hereditary Exostoses___I need more time than other kids to take exams or And Their Familiescomplete homework because of my MHE. 14 Stony Brook Drive, Pine Island, NY 10969 – mheandme@yahoo.comChapter Five 3 Section Three
  • 134. Chapter Five 4 Section Three
  • 135. Chapter Six – Chondrosarcoma Section One A Patient’s Guide to ChondrosarcomaContributor: Elizabeth Munroz, Author and Webmaster of "A PatientsGuide to Chondrosarcoma Website" (;Moderator, Yahoo Chondrosarcoma Support Group; Founder andWebmaster of website outlining her personal story of MHE andChondrosarcoma. Reprinted with permission of the author.
  • 136. A PATIENTS GUIDE TO CHONDROSARCOMA(The following is a copy of the website located at QUESTIONSThis site is being maintained by a patient who has survived Chondrosarcoma. I am not aphysician. I have no medical professional degree. I am a layperson, a patient, who haslong term survival, and no recurrence of Chondrosarcoma for many years. I have learnedmany things along the way about Chondrosarcoma. I am sharing here what I have learned,and providing as much information as possible to the best of my ability, andunderstanding.It can be very confusing to research Chondrosarcoma. There are so many kinds ofSarcoma, and one can get confused sorting out the facts. Some of my doctors have taughtme a great deal. I have attended college courses, including pre-med. I have learned toresearch considerably. I hope to save others from having to spend their lives trying tolearn about Chondrosarcoma on their own. If I can help just one person to get throughtheir experience with Chondrosarcoma, then all my years of going through it alone, andnever knowing another soul with the same diagnosis, will have been worth it. Thefollowing questions are answered.1) Whats the difference between healthy bone and Chondrosarcoma?2) What is Chondrosarcoma?3) What are the possible risks of developing Chondrosarcoma?4) What are the symptoms of Chondrosarcoma?5) What locations in the body are chondrosarcoma tumors commonly found?6) Where is the best place to go to receive appropriate medical treatment?7) What are the methods used to diagnose chondrosarcoma?8) What is tumor staging for chondrosarcoma?9) What are the different kinds of Chondrosarcoma?10) What are the chances for full remission, cure and survival?11) What would happen if no surgery is done to remove chondrosarcoma?12) What about Radiation and Chemotherapy for Chondrosarcoma?13) Is support available for Chondrosarcoma patients?Chapter Six 1 Section One
  • 137. 14) What are the possible long-term physical effects of Chondrosarcoma?15) What alternative methods of treatment are known to be successful in curingchondrosarcoma?16) Who is the person that created this site?CHONDROSARCOMA QUESTIONSWhat is Chondrosarcoma?Chondrosarcoma is a disorder of bone growth (tumor) that is different from the normalcondition of the bone. Chondrosarcoma is common to humans as well as animals. Peoplewho have chondrosarcoma have a tumor growth, or malignant bony type of bump, whichcan vary in size, and location depending on the individual affected. Chondrosarcomausually develops from normal cartilage, but it may also form within benign tumors ofcartilage and bone called osteochondromas A Chondrosarcoma is not benign. This is acancer of cartilage cells, and is the second most common primary bone cancer.Chondrosarcoma is malignant. It is a tumor in which cancer (malignant) cells begingrowing in cartilage tissue within or on the bone (central chondrosarcoma) or secondarilywithin the cartilaginous cap of a pre-existing osteochondroma (peripheralchondrosarcoma). Chondrosarcoma can be referred to by various names depending on thetype of cells identified by looking at them under a microscope.It is important to understand the difference between a benign and malignant bone tumor.A chondroma, exostosis or enchondroma, is a benign bone tumor. Benign bone tumorsare not sarcomas. Benign bone tumors do not spread to other tissues and organs, and arenot life-threatening. They are generally cured by surgery. Types of benign bone tumorsinclude osteoma, osteoid osteoma, osteoblastoma, osteochondroma, (also known asexostoses) hemangioma, and chondromyxoid fibroma. These are not malignant.Malignant tumors arising from the skeletal system are rare, representing only two/tenthsof a percent of all new cancers. Approximately 2100 new cases occur in the United Stateseach year. The most common type of bone cancer is osteosarcoma, which develops innew tissue inside growing bones. Chondrosarcoma arises in cartilage. Evidence suggeststhat Ewings sarcoma, another form of bone cancer, begins in immature nerve tissue inbone marrow. Osteosarcoma and Ewings sarcoma tend to occur more frequently inchildren and adolescents, while chondrosarcoma occurs more often in adults.Chondrosarcoma is not the type of cancer that has spread from other organs to the bone.That is called metastatic bone cancer which did not start in the bone. A typical example iswhen lung, kidney, liver, breast or other cancer spreads to the bones as part of metastasis.Examination of the cells of metastatic bone cancer look like lung cancer cells, (or liver,breast etc.) not true bone cancer cells, even after they have spread from the lungs to thebones.Chapter Six 2 Section One
  • 138. Chondrosarcoma should not be confused with Osteosarcoma which is also calledosteogenic sarcoma. Osteosarcoma is a cancerous tumor within the bone itself, (not thecartilage) and is the most common primary bone cancer. Although osteosarcoma mostoften occurs in young people between age 10 and 30, about 10% of cases develop inpeople in their 60s and 70s. Osteosarcoma is rare during middle age. More males thanfemales get osteosarcoma. These tumors develop most often in bones of the arms, legsand pelvis.Chondrosarcoma has a better outcome than osteosarcoma. The treatment options for boththese cancers are different. Treatment for chondrosarcoma is usually less invasive thantreatment for Osteosarcoma. Treatment for chondrosarcoma commonly only involvessurgical removal of the tumor and surrounding tissue. Recurrence rates forchondrosarcoma are less than osteosarcoma. Chemotherapy and Radiation treatments aremore frequently necessary in osteosarcoma and not in chondrosarcoma. The percentagefor full recovery in chondrosarcoma patients is much higher than in osteosarcoma.These are other types of bone cancer which are NOT chondrosarcomaEwings tumorFibrosarcomaMalignant Fibrous HistiocytomaGiant cell tumor of boneChordomaLymphomasKaposis SarcomaMultiple MyelomaWhat are the possible risks of developing Chondrosarcoma?It is not contagious. It cannot be passed on to another person by exposure to achondrosarcoma patient. Although scientists are not certain what causes chondrosarcoma,a number of factors may put a person at increased risk.Chondrosarcoma is a condition that sometimes has a genetic component. Certainhereditary conditions are more likely to be susceptible. Chondrosarcoma is more likely todevelop in people who have specific pre-existing genetic conditions, such as Olliersdisease, Maffucci Syndrome and Multiple Hereditary Exostoses or Osteochondromatoses.People affected by these conditions are more susceptible because they have alreadyexisting benign bone tumors (sometimes mistakenly called bone spurs) which have achance of becoming malignant. People with these hereditary conditions who experiencesudden growth spurts or increases in hormone production, such as pregnancy, have aslight increased possibility of a primary benign bone tumor changing into achondrosarcoma and should be followed by a Bone Tumor Specialist all their lives.Recently, chromosomes in the genes have been shown to have specific locations wherethe genetic information for chondrosarcoma resides. Continuing research of the genes andhow the proteins encode for them will give tremendous insight into the growth of cells.This information is important since chondrosarcoma is a problem with the growth of cells.Understanding the gene and the function of its protein might eventually provide theknowledge leading to better treatment. Some researchers feel there actually may be hopesChapter Six 3 Section One
  • 139. that genetic manipulations could treat or prevent chondrosarcoma and may be possible inthe future.The gene mapping studies will serve as the basis for the testing of patients at risk forchondrosarcoma. Information from this kind of testing could lead to the prevention of thedevelopment of Chondrosarcoma. And it is hoped that physicians could be equipped toperform such tests in the future.However, there are Chondrosarcoma patients who do not have any of these geneticconditions. Some researchers report that a previous traumatic injury to the bone can be apossible suspected cause for Chondrosarcoma, but so far this idea is not entirelyscientifically proven. Also, there is some evidence that environmental exposure can pre-dispose a person to chondrosarcoma. An example of this known possibility is exposure tocarcinogenic chemicals, gardening chemicals, as well as heavy doses of radiationexposure usually performed on patients with other previous forms of unrelated cancer.Adults with Pagets disease, a non-cancerous condition characterized by abnormaldevelopment of new bone cells, may be at increased risk for osteosarcoma orchondrosarcoma. When chondrosarcoma occurs in children and young adults, it is usuallythose who have had radiation or chemotherapy treatments for other conditions.What are the symptoms of Chondrosarcoma?The first symptom may be a solid mass or lump. Pain is often a common symptom ofchondrosarcoma. Although some patients do not experience pain and their tumor isdiscovered quite by accident. Symptoms of chondrosarcoma may vary depending on thelocation and size of the cancer. If the mass interferes with a function of the body, it maycause other feelings such as pressure against other organs in the area of location. Tumorsthat occur in or near joints may cause swelling or tenderness in the affected area andinterfere with normal movements and can weaken the bones, occasionally leading to afracture. Often chondrosarcoma goes undiagnosed or misdiagnosed at first because thesymptoms can mimic other conditions. There can be sciatic-like pain if located in thepelvis or thighs. Nerve damage or vascular compromise can occur when a tumor ispressing on them, too.The primary symptoms of chondrosarcoma do NOT cause symptoms of fever, fatigue,hair loss, weight loss, or night sweats the way that some other cancers do. These type ofsymptoms may develop if the chondrosarcoma patient goes through chemo or radiation.What locations in the body are chondrosarcoma tumors commonly found?Chondrosarcomas may develop in any part of the body, but most are commonly found inthe pelvis, rib cage, arms, and legs. Although any bone can be affected, the long bones(legs, arms, fingers, toes,) pelvis and shoulder blades are the most common. While theface and skull are generally unaffected, it is not unheard of. Occasionallychondrosarcoma has been found in the spine, or skull. It is extremely rare to findchondrosarcoma in any internal organs. If Chondrosarcoma metastasizes, it usuallyspreads to the lung.Chapter Six 4 Section One
  • 140. Where is the best place to go to receive appropriate treatment?The majority of patients with chondrosarcoma are best treated at major SARCOMAcenters with special diagnostic facilities and Musculoskeletal Tumor Specialists orOrthopedic Oncologists available. Because many bone cancers are not common, it isoften a good idea to seek an opinion from a major cancer center that has a wideexperience in treating bone cancers. This is where you will find organized groups ofdoctors and other health care professionals who work together to provide the besttreatment options and recovery.If your primary care physician suspects chondrosarcoma, a simple referral to anOrthopedic doctor may not be your best option, even with an HMO. Be sure to ask yourdoctor what his qualifications and credentials are as a "Bone Cancer Specialist."Obtaining a second opinion can provide more accurate information and help you feelmore confident about the treatment plan that is chosen for the future condition of yourmedical well-being. Most insurance companies require a second opinion before they willagree to pay for treatments, anyway. You are entitled to a second opinion.Remember that you have a right to a second opinion. You may find it helpful to discusschondrosarcoma with an Orthopedic Tumor Specialist who has the most up to date factsabout your disease at a major medical center. If you cannot find one in your area, call amajor University Medical Center and ask for a recommendation.What kinds of doctors are most qualified to treat chondrosarcoma?Orthopedic doctors who are Bone Tumor Specialists. Their specialty designates them asMusculoskeletal Tumor Specialists or Orthopedic Oncologists. What other kinds ofmedical staff are involved in diagnosing and treating chondrosarcoma?Orthopedic OncologistMusculoskeletal Tumor SpecialistNeurosurgeon (if tumor is located in skull or vertebrae)Thoracic Surgeon (if tumor is located within rib cage)Oncological RadiologistProton Beam RadiologistPathologistPhysical TherapistProthetistWhat are the methods used to diagnose chondrosarcoma?If a patient has symptoms of a chondrosarcoma, the doctor may need to perform aphysical examination based on the symptoms described by the patient. If the patient has afirm, soft-tissue mass attached to the underlying bone with pain or tenderness, this maybe an indication to suspect Chondrosarcoma. Recent noticeable growth of a lump, painand swelling are often the most common complaint. Sometimes, however, there is noChapter Six 5 Section One
  • 141. obvious evidence of pain and the diagnosis can be confused. There is usually no swellingin any adjacent joint, and range of motion is usually normal, unless tumor has grownlarge enough to cause a problem. Fracture of the involved bone is rare. However, in somepatients this is the first indication that chondrosarcoma may be present. Systemicsymptoms can be associated with the size and location of the tumor. For example, pelvictumor can present with sciatica, numbness or tingling, extra bladder pressure, bowel ormenstrual problems. Tumor located in the rib cage can cause pressure upon the lungs,heart, liver or stomach.In order to determine the diagnosis properly, the doctor may order x-rays and other testssuch as a CAT scan, MRI or bone scan. One of these tests, alone, is not enough todetermine the diagnosis. So, a combination of these tests helps to reveal the size andcharacteristics of the tumor and adjacent tissue.The Radiologist may detect changes consistent with Chondrosarcoma which is most oftenpresent on x-ray film as ill-defined lesions with a moderate-sized to large soft tissuecomponent and often demonstrating calcified cartilage. Cat Scan, MRI, Bone Scan, andUltrasound will give further clarification, and definition of the tumor, and/or in order todetermine if other organs are involved.What do Radiologists look for in a bone scan?(paraphrased from"Benign Osteochondroma (exostosis) may show normal to dramatically increased boneuptake. Osteochondroma (benign bone tumor) is relatively uncommon in the spine (1-4%occur in the spine and account for 4% of solitary primary spine bone tumors).Normal to mild uptake in an exostosis generally excludes malignancy. However, markeduptake is not specific for malignant degeneration. More intense uptake is seen in growingchildren. Fracture, of course, results in intense uptake. Thus, the role of bone scan inexostosis or multiple hereditary exostosis is questionable.Thin-slice CT may provide the diagnosis if marrow and cortical continuity can bedemonstrated. MRI will show the characteristic cartilaginous cap (intermediate on T1-and high on T2-weighted images). If this cap is greater than 1 to 2 cm in thickness,concern must be raised of chondrosarcoma.Chondrosarcoma, the second most common malignant spinal primary bone tumor, is adestructive, lytic tumor with a chondroid matrix consisting of "rings and arcs"radiographically. Cortical destruction is always present (excluded by CT in this case). Asoft tissue component is common. In bone scan, these produce patchy or homogeneousincreased uptake."According to an article entitled:Enchondroma and Chondrosarcoma in Seminal Musculoskeletal Radiology2000;4(1):59-71 By Flemming DJ, Murphey MD PMID: 11073818, UI: 20527950Chapter Six 6 Section One
  • 142. "The judicious use of computed tomography, magnetic resonance imaging, and nuclearmedicine in conjunction with appropriate clinical data allows the radiologist to establishthe correct diagnosis of benign or malignant medullary chondroid lesion in the majorityof cases."There are no blood tests available at this time useful for diagnosing Chondrosarcoma.Blood tests will eliminate the possibility of other kinds of bone cancer.Once sufficient studies have been done, the doctor may also cut out a small piece oftissue and have a pathologist look at it under the microscope to see if there are any cancercells. This is called a biopsy.What is tumor staging for chondrosarcoma?Once chondrosarcoma is found, biopsy tests will be done to find out if the cancer cellshave spread to other parts of the body. This is called staging. The doctor needs to knowthe stage of the cancer in order to plan treatment.There are several staging systems for chondrosarcoma, but no single staging systemapplies to all types of this cancer. The treatment options in this summary are based onwhether the cancer has spread or the amount of tumor left after surgery. The general nonspecific stages of chondrosarcoma are non-metastatic, metastatic, and recurrent.Treatment by stageIf the Chondrosarcoma is stage I or II the treatment option may simply be surgery toremove all of the cancer. Patients may undergo close monitoring with CT scans on aregular basis to be sure the tumor does not place any vital organs in danger, or ifcomplete removal of the tumor is not possible, or if the tumor comes back followingsurgery. Sometimes a second operation must be done to be sure that all the tumor hasbeen removed, or if the tumor comes back following treatment. No recurrence of tumorafter five years is considered to be cured.What are the different kinds of Chondrosarcoma?Chondrosarcoma can be classified in the following ways depending on location of thetumor in the body, and the type of cells located in the tumor, as determined by thePathologist.Conventional ChondrosarcomaClear CellDe-differentiatedExtraskeletal Myxoid ChondrosarcomaExtraskeletal Mesenchymal Chondrosarcoma(to get further descriptions of these google search may be useful as well as a search onPubMed)Chapter Six 7 Section One
  • 143. 1. Nonmetastatic chondrosarcomaThe cancer is found only in the area where it started and has not spread to other parts ofthe body.2. Metastatic chondrosarcomaThe cancer has spread from where it started to other parts of the body, in most cases, thelung.Patients who have metastatic chondrosarcoma may receive combined chemotherapy,radiation therapy, and surgery to remove the cancer that has spread.3. Recurrent chondrosarcomaThe cancer has come back (recurred) after it has been treated. It may come back in thearea where it started or (in rare circumstances) in another part of the body.Treatment for recurrent chondrosarcoma depends on treatment received previously, theoriginal biopsy staging results, the part of the body where the cancer has come back, andgeneral condition of the patient. Amputation is sometimes necessary.What is the possibility of recurrence?Once removed, chondrosarcoma can reoccur, but may not immediately re-grow to a sizelarge enough to be symptomatic or as noticeable as the original tumor. It is veryimportant to have follow-up appointments with the doctor in order to keep track of anyfurther re-growth. Follow up should include Cat Scans. The distinction between arecurrence in the same location and recurrence in a different part of the body makes animportant difference. A recurrence in the same location as the original tumor isconsidered to be a non-metastatic chondrosarcoma. A recurrence in a different part of thebody is considered metastatic chondrosarcoma, and more serious.What are the chances for full remission, cure and survival?The chance of recovery, (prognosis) depends on the type, location, and stage of the tumor.The chance of recovery also depends on the age, size of the tumor, stage of development,and general health of the patient.In the year 2000, about 2,500 new cases of cancer of the bones and joints were diagnosed,and about 1,400 deaths from these cancers were the expected outcome. Primary cancersof bones account for less than 0.2 percent of all cancers.What are the percentages of cancers that are bone cancers?Osteosarcoma is the most common primary bone cancer (35% of cases)followed by chondrosarcoma (26%)Chapter Six 8 Section One
  • 144. Ewings tumor (16%)chordoma (8%)malignant fibrous histiocytoma/fibrosarcoma (6%)Several other more rare cancers account for the remainder of cases.The long term prognosis for people with primary bone cancer varies greatly, dependingon the specific type of cancer and how far it has spread. If you have questions about yourpersonal chances of cure of bone cancer, or how long you might survive such a cancer, itis always best recommended to talk with the people who know your uniquecircumstances best - your Musculoskeletal or Orthopedic Oncology care team.What would happen if no surgery is done to remove chondrosarcoma?Chondrosarcoma will continue to grow and become more aggressive, the longer it is leftin the body. Depending on the location in the body, it can cause considerable problemswith other organs. Chondrosarcoma on the rib cage, for example, can grow to the point ofpuncturing a lung or causing problems with the heart. Chondrosarcoma in long bone,such as a leg or arms, can eventually cause spontaneous fracture. Chondrosarcomalocated close to the joints can cause separation of the joints. Untreated chondrosarcomacan cause tears in muscle or ligaments, cause severe nerve damage with numbness orprevent blood from flowing properly through the vasculature resulting in clotting orcrippling. Untreated Chondrosarcoma, depending on the staging, can be so aggressive asto cause death.What about Radiation and Chemotherapy for Chondrosarcoma?Radiation and Chemotherapy are not common methods of treatment for Chondrosarcoma.Only rarely are radiation and chemotherapy used on a patient with Chondrosarcoma. Thedecision to do so, depends on the advanced staging of the tumor and the type. Moreaggressive forms of Chondrosarcoma are given the designation of Stage III and Stage IV.If it is considered to be an aggressive or advanced chondrosarcoma, chemotherapy orradiation may be considered as part of the treatment plan.If you are not being treated by a Musculoskeletal Oncologist (Bone Tumor Specialist)question your doctor as to why one is not included in your medical care. Ask whyradiation or chemotherapy is being offered and what medical evidence there is forusefulness of such treatment for chondrosarcoma. Ask if you are being offered radiationor chemotherapy as part of a research protocol.Very rarely, if the Chondrosarcoma is dedifferentiated, then radiation therapy, orchemotherapy to reduce the tumor size may be followed by surgery to remove the cancer.Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be taken by mouth inthe form of a pill, or it may be put into the body by a needle in a vein or muscle.Chemotherapy is called a systemic treatment because the drugs enter the bloodstream,travel through the body, and can kill cancer cells throughout the body.Chapter Six 9 Section One
  • 145. Radiation therapy uses high-energy rays to kill cancer cells and shrink tumors. Radiationmay be given before surgery or following surgery, if the surgeon is unable to removeadequate tissue surrounding the tumor. Radiation may come from a machine outside thebody (external radiation therapy) or from putting materials that produce radiation(radioisotopes) through thin plastic tubes into the area where the cancer cells are found(internal radiation therapy).Is support available for Chondrosarcoma patients?Since it is a rare condition, there are not a lot of people available to form a local supportgroup in your neighborhood or town, even your city. As a person with cancer, it would beappropriate to participate in other types of cancer support groups, if you choose. But theuniqueness of Chondrosarcoma has a tendency to make one feel isolated and confusedwhen communicating with patients with other kinds of cancers. Chondrosarcoma patientscan join together online and share their unique experiences through the Yahoo"Chondrosarcoma Survival Support Group", which is Moderated by the author of thiswebsite.Yahoo will require you to get a yahoo ID if you dont already have one. Applying formembership does not automatically admit you to the group. You will be required toprovide identifying information to the Moderator before being accepted into the group.This is to protect the privacy of all members.If you have questions about the process required for joining the online support group or,if you do not have online access you may contact the author of this web site, ElizabethMunroz by calling (831) 786-9795An example of most supports groups:When you have a well known condition such as heart disease, or diabetes you can pick upjust about any magazine to read the latest article on the subject. You can turn on thetelevision and the evening news will give a spot to your condition. Your local hospitals,community centers or adult schools offer classes on how to improve your chances forsurvival. You can always find a support group with real people participating in them rightthere in your own home town. There is a large proportion of the population with thesewell known conditions who can make contact, enjoy one anothers company, shareknowledge and information regarding their condition and support one another through thehard times.But, you dont have these opportunities for knowledge and understanding ofChondrosarcoma. Not only do you NOT find articles in magazines, news reports,educational classes or support groups, but in all likelihood, you will not find anothersingle person in your daily life with the diagnosis of chondrosarcoma. (The exceptionnow is the internet.) Even most doctors are not very knowledgeable aboutChondrosarcoma.Chapter Six 10 Section One
  • 146. Why is there so little information available about chondrosarcoma as compared toother kinds of Cancer?Chondrosarcoma is a rare condition, even though it is the second most prevalent form ofbone cancer.Rare conditions do not get the attention that more common diseases do from the medicalestablishment.Rare conditions do not get a lot of funding for research.Rare conditions are often referred to as "orphan diseases".The average Family Physician and some Oncologists and Orthopedic doctors areprobably completely unfamiliar with chondrosarcoma, and how to diagnose it and treat it.Before the internet, it was difficult to find information for the public reader on the subjectof chondrosarcoma. Medical research articles on it were only found in Orthopedicmedical journals, and occasionally in other specialty periodicals when a patient withchondrosarcoma had it located in a part of the body affecting another specialty.Even now, with the internet, the plethora of other articles and medical informationregarding other conditions is like day at the beach in comparison to articles available onchondrosarcoma, which are like finding a particular grain of sand. A good source forinformation on chondrosarcoma is PubMedWhat are the long term physical effects of Chondrosarcoma?Sometimes chondrosarcoma grows near nerves or tendons and press on them. Surgicalremoval of the tumor is imperative so damage wont occur to the nearby structures. Dueto the necessity of complete removal of chondrosarcoma to prevent metastasis a largeamount of body tissue may be affected, including possible partial amputation.Improvements in proper medical care for chondrosarcoma patients often include limb-sparing techniques which may prevent such outcomes. Other possible long term effects ofchondrosarcoma are:PainScarsDeformityNerve damageEarly onset of Degenerative OsteoarthritisBio-mechanical and musculoskeletal problemsDepressionAnxietyPost Traumatic SyndromeChapter Six 11 Section One
  • 147. What alternative methods of treatment are known to be successful in curingchondrosarcoma?There are no known alternative treatments to cure chondrosarcoma. None. If the readershould happen to have substantiated proof of an alternative cure for this rare cancer,please inform the web author.The most effective method of treating chondrosarcoma to prevent recurrence or possiblycreate a cure is ablative surgery with clear margins.However, if you are considering any alternative or complementary treatments, discussthis openly with your cancer care team. Oftentimes they are open minded to the fact thata patient may want to include a complementary method to help recovery. However, justbecause a friend tells a fantastic story of cure, doesnt mean that it is fact. Arm yourselfwith knowledge and sort out the facts from the fiction. Request information from theAmerican Cancer Society or the National Cancer Institute. Do as much research where you can to document the usefulness of whatever alternativetreatments you may be considering. There is scientific research on complementarytreatments. Just because someone writes up a webpage touting a cure with some claimsthat patients have supposedly made of success, does not give you true medical evidenceof the facts. Ask yourself if you are desperate, or hopeful in regards to attempting suchmethods. If you are desperate, then please be careful. Dont be gullible. Dont allow yourjudgment to be swayed by the idea of avoiding surgery, or whatever treatment yourphysician is suggesting. Some alternative treatments can be a useful adjunct to a patientreceiving traditional treatment. Yet, some alternative treatments can interfere withstandard medical treatments or may cause serious side effects. Be well informed aboutyour choices.Chapter Six 12 Section One
  • 148. A PATIENTS GUIDE TO CHONDROSARCOMA CHONDROSARCOMA QUESTIONSWho is the person who created this site? Elizabeth MunrozBorn in Buffalo, New York, Elizabeth presently lives in Watsonville, California. She wasborn with a genetic condition called Hereditary Multiple Exostoses, which includeshaving many benign cartilage bone tumors. As a young woman, one of those tumorstransformed into a malignancy called Chondrosarcoma. This was located in the pelvis.She had seven recurrences from 1967 to 1980. With such long term survival, she wantsvery much to encourage others with the diagnosis to have hope. She is the Moderator ofthe Yahoo Chondrosarcoma Support Group she set up a website outlining her story of MHE and Chondrosarcoma, she has hadcontact with many people from all over the world with the same can be contacted by email at the following sure you put "Chondrosarcoma Question" in the title of the email, so she won’tmiss your message.)If you wish to make contact about Chondrosarcoma by telephone, Elizabeth willwelcome your call between Noon and 10 pm Pacific Time at (831)786-9795Chapter Six 13 Section One
  • 149. A PATIENTS GUIDE TO CHONDROSARCOMAThis site was created in loving memory of Raj A. Megha.Disclaimer:This material should not be used as a basis for treatment decisions, and is not asubstitute for professional consultation. It is further recommended that patients andlaypersons looking for guidance among the sources of this webpage are strongly advisedto review the information with their professional health care provider.copyright 2001 by Elizabeth Munroz All rights reserved.Chapter Six 14 Section One