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Congenital Malformations of Bone


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For Orthopaedicians and UnderGraduates

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Congenital Malformations of Bone

  1. 1. Congenital Malformations Of Bone (Skeletal Dysplasia) Dr. Apoorv Jain D’Ortho, DNB Ortho +91-9845669975
  2. 2. • The Word dysplasia originates from the ancient greek words dys(anomalous) & plasia(formation) • Skeletal dysplasia is a heterogeneous group of congenital anomalies characterized by the abnormalities in the development of Bone and cartilagenous tissues
  3. 3. Normal Bone Development On the basis of development, the bones are of 2 types: • Intramembranous bones • Endochondral bones Intramembranous Ossification: Bone is directly laid down in membranous sheets without any cartilaginous model (Eg: Clavicle, Facial bones and Bones of the Skull vault)
  4. 4. Endochondral Bones: The formation of bone is preceded by the formation of a cartilaginous bone model which is replaced by bone (Eg: Bones of the limbs except clavicle, trunk and base of the skull)
  5. 5. Classification Of Skeletal Malformations (By Agerter and Kirkpatrick, 1975) 1) Disturbances in Chondroid Production: Abnormal Maturation of Chondroblasts: •Mucopolysaccharidosis •Idiopathic: –Achondroplasia –Cartilage-Hair Hypoplasia –Metaphyseal Dysostosis
  6. 6. Heterotopic Proliferation Of Chondroblasts: -Enchondromatosis (Dyschondroplasia , Ollier’s disease) -Osteochondromatosis (Multiple Heriditary Exostosis) -Epiphyseal Hyperplasia
  7. 7. 2. Disturbances in Osteoid production: A) Abnormal Epiphyseal Ossification: -Diastrophic Dwarfism -Spondyloepiphyseal Dysplasia -Multiple Epiphyseal Dysplasia (Includes Blount’s and Pseudochondroplasia) -Stippled Epiphysis
  8. 8. B) Abnormal Metaphyseal and Periosteal Ossification: 1) Deficient Osteoid Production: -Osteogenesis Imperfecta 2) Excessive Osteoid production or Decreased Osteolysis: -Osteopetrosis -Pykindysostosis -Metaphyseal Dysplasia -Diaphyseal Sclerosis -Melorheostosis -Osteopathia Striata -Osteopoikilosis
  9. 9. C) Abnormal Osteoid Production: -Polyostotic Fibrous Dysplasia -Neurofibromatosis -Congenital Pseudoarthrosis 3) Miscellaneous Dysplasias:  Marfan’s Syndrome  Apert’s Syndrome  Cleidocranial Dysostosis  Chondroectodermal Dysplasias
  11. 11. Prenatal Diagnosis • Prenatal Ultrasound– Identify lethal dysplasias –Diagnosis based on femoral length, head circumference, body ratios and fetal characteristics typical of skeletal dysplasias • Genetic analysis –Chorionvillous biopsy –Amniocentesis
  12. 12. Postnatal Diagnosis THREE CLINICAL QUESTIONS: • Is the child abnormally small or large? • Is stature proportional or disproportional? • Dysmorphic facial features?
  13. 13. • Short Limb –Achondroplasia –Hypochondroplasia –Chondrodysplasia punctata –Achondrogenesis –Thanatophoric dysplasia • Short Trunk/limb –Spondyloepiphyseal dysplasia
  14. 14. Long Bones: • The long bones in all of the extremities should be measured. • If limb shortening is present, the segments involved should be defined. • A detailed examination of the involved bones is necessary to exclude absence, hypoplasia, and malformation of the bones.
  15. 15. • The bones should be assessed for presence, curvature, degree of mineralization, and fractures. • The femur length–abdominal circumference ratio (<0.16 suggests lung hypoplasia) and femur length–foot length ratio (normal = 1, <1 suggests skeletal dysplasia) should be calculated.
  16. 16. Thorax: • The chest circumference and cardiothoracic ratio should be measured at the level of the nipples or 5th intercostal space. • A chest circumference less than the 5th percentile for gestational age (8–10) has been proposed as an indicator of pulmonary hypoplasia.
  17. 17. The chest diameter should be between 80-100% of the abdominal diameter.
  18. 18. • The shape and integrity of the thorax should be noted. • Abnormal rib size and configuration are also seen in patients with lethal skeletal dysplasias. • The clavicles should be measured, since absence or hypoplasia of the clavicles is seen in cleidocranial dysplasia. • The presence of the scapula should also be noted, since its absence is a useful defining feature of camptomelic dysplasia.
  19. 19. Hands and Feet: The hands and feet should be evaluated to exclude the presence of (a) Polydactyly (the presence of more than five digits) [Preaxial if the extra digits are located on the radial or tibial side and postaxial if they are located on the ulnar or fibular side] (b) Syndactyly (soft-tissue or bone fusion of adjacent digits). (c) Clinodactyly (deviation of a finger) and other deformities.
  20. 20. Example Of Post-axial Polydactyly
  21. 21. Bony Syndactyly Clinodactyly
  22. 22. • “Radial-ray” anomalies range from abnormal thumbs to hypoplasia or absence of the thumb and sometimes absence of the radius or even the radius and the hand. • The three most likely diagnoses include: Holt-Oram syndrome, the thrombocytopenia- absent radius (TAR) syndrome and trisomy 18.
  23. 23. Skull: • Head circumference and biparietal diameter should be measured to exclude macrocephaly. • The shape, mineralization, and degree of ossification of the skull should be evaluated. • Interorbital distance should be measured by using the binocular diameter and interocular diameter to exclude hyper- or hypotelorism.
  24. 24. Normal Skull Scaphocephaly Brachycephaly
  25. 25. Craniosynostosis seen in conditions like: Thanatophoric dysplasia, Carpenter's syndrome, Hypophosphatasia, Crouzon – Aperts. Wormian bones seen with Cleidocranial dysplasia, Osteogenesis imperfecta, Trisomy 21, Hypothyroidism, Progeria.
  26. 26. Spine: • The spine should be carefully imaged to assess the relative total length and the presence of curvature to exclude scoliosis. • Mineralization of vertebral bodies and neural arches should be evaluated. • Vertebral height should be subjectively evaluated for platyspondyly (flattened vertebral body shape with reduced distance between the endplates), which is typically seen in thanatophoric dysplasia.
  27. 27. Pelvis: • The shape of the pelvis can be important in certain dysplasias, such as limb-pelvic hypoplasia. • Femoral hypoplasia–unusual face syndrome (hypoplastic acetabulae, constricted iliac base with vertical ischial axis, and large obturator foramina). • Achondroplasia (flat, rounded iliac bones with lack of iliac flaring; broad, horizontal superior acetabular margins; and small sacrosciatic notches).
  28. 28. University of Washington Medical Center Worksheet while evaluating a patient suspected skeletal dysplasia
  29. 29. RADIOGRAPHIC EXAMINATION: • A complete skeletal survey should be done in children >6 months. • In newborns and infants <6 months, at least –AP and lateral films of the whole spine –AP films of the hands –Lateral skull –Lateral cervical spine flexion and extension
  30. 30. Hypoplastic scapulae in campomelic dysplasia Thoraco Lumbar Kyphosis as seen in Achondroplasia and Sponyloepithelial dysplasia
  31. 31. Cervical Instability (Can be seen in every dysplasia except Achondroplasia)
  32. 32. Cervical Instability on MRI
  33. 33. Platyspondyly and Thickened, Shortened small bones commonly seen in Mucopolysaccharidosis
  34. 34. Final Diagnosis • Prenatal/Postnatal onset • Skeletal features –short limb/short trunk –acro, meso or rhizomelia • Extra skeletal features • Family history • Radiographic characteristics • Laboratory • Genetic analysis
  35. 35. Skeletal dysplasias include more than 380 conditions leading to abnormally developed bones and connective tissues
  36. 36. Osteogenesis Imperfecta
  37. 37. Synonyms • Fragilis osseum • Osteopsathyrosis idiopathica • Brittle Bone disease • Glass Bone disease • Periosteal dysplasia • Lobstein’s disease • Vrolik disease • Porak and Durante’s disease
  38. 38. Introduction • It is a genetic disorder of connective tissue with clinical features of increased bone fragility • It maybe inherited as Autosomal Dominant or may occur as spontaneous mutation or rarely inherited as a homozygous Autosomal Recessive trait
  39. 39. Introduction… • Major clinical features include Skeletal deformity, Blue sclerae, Fragile opalescent teeth (Dentinogenesis imperfecta) • Less severe manifestations include generalised ligamentous laxity, hernias, easy bruisability and excessive sweating
  40. 40. Normal Collagen Metabolism • Collagen is a connective tissue protein with a left handed triple helical structure • Type I Collagen composed of 2 α1(I) strands and 1 α2(I) strand • In fibroblasts the precursors are synthesized in RER – Pro α1(I) encoded by COL1A1 on Chr. 17 – Pro α2(I) encoded by COL1A2 on Chr. 7
  41. 41. Normal Collagen Metabolism • 2 Pro α1(I) + 1 Pro α2(I)  type I Procollagen beginning at the C end and propagating towards the Amino terminal • Cross linking - Gly residues; every 3rd position • Type I Procollagen is secreted from the cells and processed extracellularly to form Type I Collagen molecule
  42. 42. Collagen Metabolism in OI • 90% have an identifiable genetically determined defect, either qualitative or quantitative, in type I Collagen formation • Assayed from cultures of fibroblasts from skin biopsies using electrophoresis
  43. 43. Classifications • Looser (1906) classified into two types Congenita – Numerous fractures at birth Tarda – Fractures after perinatal period • Shapiro subclassified either of these categories into Type A and Type B
  44. 44. • Shapiro’s classified OI into 4 types based on prognosis for survival and ambulation OI Congenita A Fractures in utero or at birth Still born or die shortly after birth OI Congenita B Fractures at birth Long bones are more tubular and more normal funnelization in the metaphysis OI Tarda A Onset of fractures prior to walking OI Tarda B First fracture after walking
  45. 45. Type I Type II Most Common, AD Quantitative defect Mild form Distinct blue sclerae throughout life Premature arcus senilis Presenile conductive Hearing Loss ? AR, Most severe form Severe qualitative defect Extreme bone fragility Death in perinatal period or early infancy Crumbled long bones Marked delay in ossification of skull bones Sillence and Dank – 4 types (Clinical & Genetic characteristics) IA – Normal Teeth IB – with Dentinogenesis imperfecta
  46. 46. Type III Type IV AR or Dominant Negative Qualitative & quantitative defect Severe bone fragility Multiple fractures, deformities Severe growth retardation Sclerae are bluish at birth, become less blue with age and attain normal hue in adolescence AD Qualitative & quantitative defect Sclerae are usually normal hue at birth Sillence and Dank – 4 types (Clinical & Genetic characteristics) IVA – Normal Teeth IVB – with Dentinogenesis imperfecta
  47. 47. Histopathology • Bone trabeculae are thin and lack an organized trabecular pattern • The spongiosa is scanty and intercellular matrix is reduced • Tetracycline labeled studies confirm increased bone turnover
  48. 48. Clinical Features (Severe form) • Multiple fractures from minimal trauma • Deformed and short limbs • Soft and membranous skull • Usually fatal • Death secondary to IC hemorrhage or respiratory insufficiency
  49. 49. Clinical Features (Non Lethal forms) • Increased fragility of bones (earlier the fracture, more severe the disease) • Lower limbs are most commonly affected • Femur more commonly affected than tibia • Fractures heal at a normal rate • Non-union is relatively rare • Frequency of fractures decline sharply after adolescence although it may rise again in postmenopausal women
  50. 50. • Bowing of long bones • Coxa vara • Short stature • Hypermobility of joints • Hypotonic muscles • Thin and translucent skin, subcutaneous hemorrhages • Excessive sweating due to resting hypermetabolic state • Heat intolerance • Metabolic acidosis • Cardiac arrhythmia
  51. 51. Skull • Forehead broad with prominent parietal and temporal bones and overhanging occiput • Triangular elfin shaped face • Ears are displaced downwards and outwards • The configuration of Skull in OI is called ‘Helmet head’
  52. 52. • Severe spinal deformities (Scoliosis and Kyphosis) – Osteoporosis – Compression fractures – Ligamentous hyperlaxity • Scoliosis in 20 – 40% cases, Most commonly Thoracic scoliosis • Spondylolisthesis • Cervical anomalies Spine
  53. 53. • Blue Sclerae • Saturn’s ring • Hyperopia • Arcus juvenilis • Retinal detachment • Deafness (40% in Type I, less in Type IV) – Conductive – Otosclerosis or – Nerve deafness Eye Ear
  54. 54. • Dentinogenesis imperfecta (Hereditary Opalescent Dentine or Hereditary hypoplasia of dentine) • In Type IB and Type IVB • Enamel normal; teeth break easily – prone to caries • Lower incisors, which erupt 1st most severely affected Teeth
  55. 55. Radiologic Features Severe Form • Short long bones with thin cortices • Wide diaphysis • Numerous # in various stages of healing • Multiple rib # and atrophy of thoracic cage • Goldman described ‘popcorn’ calcification in the metaphysial and epiphysial area (resolves after completion of skeletal maturity)
  56. 56. Radiologic Features Severe Form Skull • Mushroom appearance with thin calvarium • Delay in ossification • Wormian bones
  57. 57. Radiologic Features Severe Form Spine • Osteoporosis • Compression # • Biconcave compressed vertebral bodies in between bulging discs • Kyphoscoliosis
  58. 58. Radiologic Features Milder Forms • Similar picture of osteoporosis • Bowing • Fractures in various stages of healing • Callus typically wispy but on rare occasions, it maybe very large and hyperplastic resembling Osteosarcoma
  59. 59. Hyperplastic Callus & Tumors in OI Clinical Features Acute localised inflammation Progressive enlargement of the limb Investigations ESR – Alk Phosphatase – X-ray – enlarging irregular callus mass Treatment Symptomatic – splinting ? Irradiation Diphosphonates
  60. 60. Final Diagnosis • Diagnosis is by –Positive family history –Clinical and radiologic findings • Type I Collagen assay • Antenatal Diagnosis – USG and Chorionic Villous Sampling
  61. 61. Treatment • No specific treatment • Rehabilitation – protective bracing and physiotherapy • Medical – Biphosphonates – Pamidronate – Gene Therapy – Bone Marrow Transplantation
  62. 62. Orthopaedic Treatment Goal • Improve function • Prevent deformity and disability • Correct deformities • Monitor for complications
  63. 63. Management Of Long Bone Fractures • Depends on severity and age of the patient • Fractures should be immobilized only until symptoms subside • As a general principle, intramedullary fixation is preferable to plate and screws whenever possible because of the stress risers produced by the later • Nonunion is rare
  64. 64. Management Long Bone Deformity • Indications for Surgery –Repeated fractures induced by the deformity –To apply bracing for either protection against further fractures or aid in ambulation • Treatment options –Closed osteoclasis without internal fixation –Closed osteoclasis with percutaneous IM fixation –Open osteotomy (fragmentation) + IM fixation - Sofield procedure
  65. 65. Management of Spinal deformity • Patient may not tolerate orthosis • Spinal fusion for severe progressive deformity • Posterior stabilisation with Luque sublaminar wires or tapes appears to be ideally suited for instrumentation in management of difficult cases
  66. 66. Blount’s Disease
  67. 67. Introduction • Tibia vara is defined as the growth retardation of the medial aspect of the proximal tibial epiphysis usually resulting in progressive bow leg. Classified into three groups as – Infantile < 3years – Juvenile 4 – 10 years – Adolescent > 10 years • Blount classified Tibia vara as – Infantile < 8 years (known as Blount’s Disease) – Adolescent > 8 years
  68. 68. Blount’s Disease • Erlacher (1922) • Blount (1937) • Synonyms –Infantile Tibia vara –Erlacher’s disease –Blount-Barber syndrome –Deformative osteochondrosis of the tibia –Nonrachitic bowleg in children –Osteochondritis deformans tibiae –Subepiphyseal osteochondropathy
  69. 69. Etiology • Familial: Autosomal Dominant inheritance • Developmental • Multifactorial: –Infection –Trauma –AVN –Latent form of rickets • Others: early weight bearing, obesity
  70. 70. Histology • The physeal cell columns become irregular and normal endochondral ossification is disrupted in the medial aspect of metaphysis and physis • Islands of nearly acellular fibrocartilage • Islands of densely packed cartilage cells with greater hypertrophy than expected from their position in the growth plate • Large clusters of capillary vessels
  71. 71. Clinical Features • Similar to physiological genu varum with 2 major differences –Usually obese and start walking early –Clinically apparent lateral thrust to the knee during the stance phase • Usually bilateral and symmetrical (60%) and varus deformity increases progressively • Varus, internal tibial torsion and genu recurvatum, plano valgus develops secondarily • Siffert – Katz sign
  72. 72. Radiological Features • Varus angulation at epiphysio- metaphyseal junction • Widened and irregular physeal line medially • Medially sloped and irregularly ossified epiphysis, sometimes triangular • Epiphysis short thin and wedged • Prominent beaking of the medial metaphysis, with lucent cartilage islands within the beak • Lateral subluxation of the proximal tibia
  73. 73. Radiological Features • According to Smith, medial metaphysial fragmentation is pathognomonic for the development of a progressive tibia vara
  74. 74. Tibio Femoral Angle Metaphysio Diaphysial angle (Levin and Drennen) MD angle
  75. 75. Other Imaging Modalities • MRI: Able to demonstrate the extent of the ossified and cartilaginous epiphysis along with any physeal anatomical disruption • Arthrography: Dalinka demonstrated hypertrophy of the medial meniscus and the unossified cartilage of the medial tibial plateau
  76. 76. CT Scan • Greene listed the following criteria for preoperative CT to determine if a bony bar is present –Age > 5 years –Medial physeal slope 50 – 70 degrees –Stage IV X-ray findings –Weight more than 95th percentile –Black female who meet the following criteria
  77. 77. Langenskiold classification (1952) • I - Irregular metaphyseal ossification combined with medial and distal protrusion of the metaphysis • II, III, IV - Evolves from a mild depression of the medial metaphysis to a step-off of the medial metaphysis • V - Increased slope of medial articular surface and a cleft separating the medial and lateral epicondyle • VI - Bony bridge across the physis Depending on degree of metaphysial and epiphysial changes on radiograph
  78. 78. Prognosis Based On Langenkiold classification • Better prognosis in earlier stages –I & II can predictably have full restoration with single osteotomy and bracing; treatment must be completed before 4 years –III maybe restored –IV – VI requires complex reconstruction and physeal procedures with guarded outcome at best
  79. 79. Treatment • Untreated infantile tibia vara generally results in progressive varus deformity, producing joint deformity and growth retardation. • Treatment choices and prognosis depend greatly on the age of the patient at the time of diagnosis.
  80. 80. Orthotics • Recommended for patients < 3 years of age and <stage II disease • Rainey et al recommended KAFO that produced a valgus force by three point pressure • Risk for failure included ligamentous instability, patient weight above 90th percentile and late initiation of bracing • Elastic Blount brace, a medial upright design with drop lock knee hinge that can be locked to increase the effectiveness of valgus pressure during weight bearing
  81. 81. Corrective Osteotomy • Beatey et al recommended valgus osteotomies of proximal tibia and fibula with mild overcorrection in young children • Early osteotomy produced best results chance of recurrence increased with increasing age
  82. 82. • Greene described Chevron osteotomy in which opening and closing wedges can be made so that the limb length deformity present in moderate to severe tibia vara will not be increased. • He described a crescent shaped osteotomy using one half lateral closing wedge and using the graft medially in an opening wedge to maintain length.
  83. 83. • In children older than 9 years with more severe involvement, osteotomy alone, with bony bar resection, or with epiphysiodesis of the lateral tibial and fibular physes may be indicated.
  84. 84. Achondroplasia
  85. 85. • Achondroplasia is a type of short- limbed dwarfism • It occurs when the process by which cartilage is converted to bone, or ossification, is stunted • This is most apparent in the long bones of the arms and legs • Incidence is 1 in 25,000 live births
  86. 86. Etiology • Autosomal dominant inheritance • Due to mutations of the FGFR3 gene on the short arm of chromosome 4 • This gene regulates bone development, so when affected, it causes malfunctions in bone growth
  87. 87. Clinical Presentation • Short arms and legs: particularly the upper arms and thighs • Enlarged head (macrocephaly) • Prominent forehead • Short fingers: the middle and ring fingers may diverge, giving the hand a three- pronged (trident) appearance
  88. 88. • Sleep apnea • Persistent ear infections • Exaggerated Lumbar Lordosis • Bowed legs • Mid-face hypoplasia • Hypotonia: low and weak muscle tone • Delays in walking and other motor skills • Back pain • Obesity • Bowed legs • Limited range of motion at the elbows
  89. 89. Diagnosis • Characteristic clinical findings • X-ray findings • Genetic analysis
  90. 90. Treatment • There is no specific or permanent treatment. • Measures to avoid obesity are taken. • To correct obstructive sleep apnea, a surgical opening in the airway, or tracheostomy, can be performed. • With patients with problems such as hyperreflexia, clonus, or central hypopnea: suboccipital decompression, which decreases pressure on the brain can be done. • Growth hormones and/or surgery may be able to lengthen limbs, but only up to a certain limit.
  91. 91. Marfan’s Syndrome
  92. 92. Description •Heritable disorder of the connective tissue •Connective tissue affects: •Growth and development •Cushioning of joints •Vital organs •1 in 5,000 people in US have disorder
  93. 93. Symptoms • Affects many body systems including: – Skeleton – Eyes – Heart and Blood Vessels – Nervous System – Lungs – Skin
  94. 94. Skeleton • Tall and slender • Disproportionately long appendages • Indented or protruding sternum • Arched palate, overcrowded teeth, receding mandible • Curvature of spine
  95. 95. Eyes • Off-center or dislocated lenses • Nearsightedness (Myopia) • Development of cataracts at a younger age (30s to 50s) • Retinal detachment • Stretch marks – Shoulders, hips, lower back • Increased risk for abdominal hernias Skin
  96. 96. Heart and Blood vessels • Weakened middle layer of aortic wall – Stretched aortic valve leaflets – Aneurysm may form • Aortic regurgitation – Left ventricle must compensate – Chest pain, heart failure • Tears in inner and middle aortic layers – Middle layer separates – New channels for blood flow
  97. 97. Nervous System • Stretching and enlargement of dura membrane – Pushes on and wears down vertebrae – Can protrude through vertebral column and into abdomen – Dural cysts • Increased susceptibility to learning disabilities
  98. 98. Lungs • Diminished alveoli elasticity • Susceptibility to asthma, bronchitis, pneumonia – In rare cases, develop emphysema • 5% experience spontaneous lung collapse • Sleep disordered breathing – Snoring most common – Caused by partial obstruction of airway by connective tissue
  99. 99. Basic Genetic Information • Autosomal Dominant • Dominant Negative Mutation – the altered gene product antagonizes the product of the normal gene • Haploinsufficiency – when a diploid organism has only one functional copy of a gene, the other copy being mutated • Affects FBN-1 Gene
  100. 100. FBN-1 Gene • Located on chromosome 15 • Codes instructions for the creation of protein Fibrillin 1 • Marfan’s is caused by over 500 different mutations on FBN1 • 60% mutations are change in one protein building block. • 40% mutations produce small protein that can’t function
  101. 101. Fibrillin 1 protein • Connect with other Fibrillin 1 proteins to make microfibrils, which become connective tissue. • Microfibrils mainly trap transforming growth factor- beta (TGF-beta) and keeps them inactive.
  102. 102. Defective Fibrillin 1 Protein • Amount of fibrillin 1 protein produced by cells is reduced • Structure and stability of protein is affected • Transport of fibrillin 1 protein out of the cell is impaired • Amount of fibrillin 1 reduced means decreased microfibril production • Less microfibril leads to more active TGF-beta, which leads to Marfan’s symptoms
  103. 103. Testing and Diagnosis • Genetic analysis: –Types •Complete bi-directional DNA sequencing •FBN1 gene sequencing •TGFBR gene sequencing •Familial mutation test
  104. 104. • Other –Imaging tests • Chest x-ray • MRI –Symptoms checklist • Family history + 2 affected body systems • At least 3 affected body systems
  105. 105. • Index case: Major criteria in 2 different organ systems AND involvement of a third organ system. Relative of index case: 1 major criterion in family history AND 1 major criterion in an organ system AND involvement in second organ system. SKELETAL Major (Presence of at least 4 of the following manifestations) __ pectus carinatum __ pectus excavatum requiring surgery __ reduced upper to lower segment ratio (Note 1) OR arm span to height ratio >1.05 Height ____ Arm span ____ Upper segment ____ Lower segment ____ __ wrist (Note 2) and thumb (Note 3) signs __ scoliosis of >20° or spondylolisthesis __ reduced extension at the elbows (<170°) __ medial displacement of the medial malleolus causing pes planus __ protrusio acetabulae of any degree (ascertained on radiographs) Minor __ pectus excavatum of moderate severity __ joint hypermobility __ high arched palate with crowding of teeth __ facial appearance __ dolichocephaly, __ malar hypoplasia, __ enophthalmos, __ retrognathia, __ down-slanting palpebral fissures Diagnostic Checklist OCULAR Major __ ectopia lentis Minor __ flat cornea __ increased axial length of the globe __ hypoplastic iris OR hypoplastic ciliary muscle causing decreased miosis CARDIOVASCULAR Major __ dilatation of the ascending aorta with or without aortic regurgitation and involving at least the sinuses of Valsalva __ dissection of the ascending aorta Minor __ mitral valve prolapse with or without mitral valve regurgitation __ dilatation of the main pulmonary artery, in the absence of valvular or peripheral pulmonic stenosis below the age of 40 years __ calcification of the mitral annulus below the age of 40 years __ dilatation or dissection of the descending thoracic or abdominal aorta below age of 50 years PULMONARY Minor (only) __ spontaneous pneumothorax __ apical blebs SKIN AND INTEGUMENT Minor (only) __ striae atrophicae __ recurrent or incisional hernia DURA Major __ lumbosacral dural ectasia by CT or MRI FAMILY/GENETIC HISTORY Major __ first degree relative who independantly meets the diagnostic criterian. __ presence of mutation in FBN1 known to cause Marfan syndrome __ presence of haplotype around FBN1 inherited by descent and unequivocally associated with diagnosed Marfan syndrome in the family
  106. 106. • Positive Steinburg Thumb Sign  Positive Walker Wrist Sign
  107. 107. Treatment • Require a multidisciplinary team • Symptoms, not disorder, must be treated • Yearly echocardiograms • Emotional support • Healthy Diet
  108. 108. Heart • Enlargement of the aorta – Aortic Dissection • Aortic Dilation – Aortic Valve regurgitation – Mitral valve prolapse • Medications – Lower blood pressure – Angiotensin receptor blockers – Beta blockers • Regular Echocardiograms
  109. 109. Skeleton • Physiotherapy • Pain Clinics –Loose joints • Bracing –Back –Ankle • Surgery –Pectus excavatum
  110. 110. Physical Activity • Avoid contact and strenuous sports because of the risk of damaging the aorta and injuring the eyes • Individual restrictions based on severity and discussed with physician
  111. 111. Apert’s Syndrome
  112. 112. • Described first by a French physician in 1906 • Also known as ACROCEPHALOSYNDACTYLIA • A genetic disorder with Autosomal Recessive inheritance • Affected gene is called FGFR2 (Fibroblast Growth Factor Receptor 2) • Locus on chromosome is 10q26
  113. 113. • All groups are affected –Most prevalent in Asians; • Incidence in Asians is 22.3 per million births • Age of onset is at birth • Diagnosed at birth itself due to peculiar features like syndactyly and shape of the skull
  114. 114. Clinical Signs • Early closure of sutures between the bones in the skull • Frequent ear infections • Fusion or severe webbing of the 2nd, 3rd, and 4th fingers –“mitten hands” • Hearing loss • Large or late-closing soft spot on a baby’s skull • Possible, slow intellectual development
  115. 115. • Severe under-development of the mid-face • Skeletal (limb) abnormalities • Short height • Webbing or fusion of the toes • Prominent or bulging eyes
  116. 116. Frequently Associated Conditions • Dextrorotation • Pulmonary Atresia • Patent Ductus Arteriosus (PDA) • Tracheoesophageal Fistula • Pyloric stenosis • Polycystic Kidneys • Ear infections • Sleep Apnea • Severe acne • Hydrocephalus • Bicornate uterus
  117. 117. Treatment -Separation of the abnormally fused skull bones to allow for the growth of the head Done in infancy -Correction of midface hypoplasia using the Ilizarov procedure Opens up the bones of the middle of the face and stimulates them to grow Done between ages 6-11 -Separation of fingers and toes
  118. 118. Correction of midface hypoplasia using the Ilizarov procedure
  119. 119. Osteopetrosis
  120. 120. • Also known as Marble bone disease and Alber Schonberg’s disease • Developmental abnormality in which the bones throughout the body become increasingly dense and brittle
  121. 121. Etiology • Defective Carbonic anhydrase function • Lack of alkaline environment for osteoclast function • Defective osteoclast function • Continued new bone deposition with no resorption • Bones are hard as marble or can be brittle like a chalk and are grey or white on cut section
  122. 122. • The medullary cavity is obliterated and deficient in bone marrow leading to pancytopenia and reduced immunity. • Bony encroachment on cranial foramina can produce optic atrophy deafness and facial paralysis.
  123. 123. Types • Infantile osteopetrosis: – Autosomal recessive – Severe form – Poor prognosis – Usually patient dies by 2 years of age • Benign adult osteopetrosis: – Autosomal dominant – Less severe form (usually detected incidentally), Good prognosis
  124. 124. Clinical Features • Shape of head (Box like appearance) • Hepatosplenomegaly • Lymphadenopathy • Optic atrophy, deafness or facial paralysis in cases with stenosis of cranial foramen • Anaemia • Pancytopenia • Frequent infections and osteomyelitis
  125. 125. Radiological features • Increased density of all bones with decreased remodelling. • Widened shafts, decreased marrow space in long bones due to increased cortical thickness. • Base of skull is thickened with narrowed cranial foramen.
  126. 126. • Paranasal sinuses : poorly pneumatized (ethmoid sinuses least severely affected) • Calvarium : high- attenuation inner table, a broad, low-attenuation diploic space, and a less high-attenuation outer table
  127. 127. Blood Routine • Anaemia • Pancytopenia • Most patients have normal levels of serum Calcium, Phosphate and Alkaline Phosphatase. • Recessive disease may have Hypocalcemia during infancy
  128. 128. Treatment • Symptomatic treatment for pain relief • Bone marrow transplantation for malignant/ lethal disease is the only treatment option
  129. 129. THANK YOU