Mucopolysaccharidoses (MPS) (Dysostosis Multiplex) The MPS dwarfs are the result of a familial genetic defect inwhich there is a deficient enzyme system that normally breaksdown the acid mucopolysaccharides in the cytoplasm ofmesenchyme cells including fibroblasts, chondroblasts and osteo-blasts. MPS inclusion bodies can be seen in these cells and acidmucopolysaccharides will be found in the urine of these dwarfs.The bony abnormalities seen early in childhood are similar tothose seen in SED congenita with short limbs and spines withkyphotic deformities. Soft tissue involvement can includeenlarged livers and spleens and clouded corneas. Mental retard-ation can result from CNS involvement. Early death can resultfrom coronary artery occlusions and heart failure. The Mucolipidoses (ML) are dwarfs with a similarenzymatic defect that prevent the catabolism of mucolipids in
mesenchyme cells resulting in the formation of inclusion bodiesseen in the cytoplasm of the various connective tissue cells. In the following slide we see a listing of all the MPS and MLconditions with the various eponyms, enzymatic defects andclinical features of each one of these various conditions.
Hurler’s Syndrome (MPS 1-H) (Gargoylism) Of all the MPS’s, Hurler’s and Morquio’s have the greatestskeletal abnormalities with short limbs and trunk. Hurler’s is anautosomal recessive disorder which becomes manifest in the firstfew years of life. They are SED congenita type dwarfs withdistinctive facies, mental retardation, deafness, corneal opacities,hepatosplenomegaly, cardiomegaly resulting in heart failure thatfrequently results in death in the first decade of life. Dermatansulfate and heparin sulfate are the acid mucuopolysacchridesfound in the urine and the enzymatic defect in Hurler’s is alpha-L-iduronidase. MPS occlusion of the normal outlet of cerebralfluid from the brain results in hydrocephaly and a characteristicboot shaped cella turcica. The universal plataspondyly of theentire spine results in LD kyphosis and atlantoaxial subluxation.We see long bone shortening with epiphyseal defects seen in
MED dwarfs with coxa valgus deformity of the hip contrastingthe coxa vara defect seen in Morquio’s. In hand x-rays we seeshortened bullet shaped phalanges with short metacarpals andmetatarsals with tapering at the base of the short bones.
Case #1 Hurler’sMentally retarded child with bushy eyebrows, depressed nasion puffy lips, hydrocephali and coxa valgum
At age 3.5 yrs we see a typical slipper defect of L-2 along with other spondyloepiphyseal defects of spine and extremities
Costochondral rib biopsy showing gargoyle foam cells in cartilage, periosteal fibroblasts and marrow tissue
Case #2 Hurler’s 6 yr mentally retarded malewith puffy lips and large tongue, hydrocephali, enlarged cella tersica and coxa valgum
Classic slipper defect of L-2 and flexion deformity of fingers (campnodactyly) and tapered proximal metacarpals
Case #3 Hurler’s 6 year old child with Hurler’s syndrome with classic hand deformity and scaphoid (keel shaped) skull due to early closureof mid sagittal suture line and coxa varum deformity of the prox. humeral epiphyses and paddle shaped ribs
Morquio’s (MPS IV) In Morquio’s we find keratin sulfate in the urine and theenzymatic defect is galactosamine-6-sulfate sulfatase. Ascompared to Hurler’s the face and skull are quite normal, butthe major problem is with spinal shortening with LD kypho-scoliosis and anterior bulging of the sternum. Odontoid hypo-plasia can result in C 1 on 2 subluxation and quadriplegia.The long bones of the extremities are shortened with flattenedand deformed epiphyses as seen in MED. Coxa varum is seenin the hip compared to the coxa valgum defect in Hurler’s. Theshort bones of the hand and feet are the same as we see inHurler’s. Corneal clouding and deafness can be seen as inHurler’s but Morquio’s patients have normal intelligence and avariable life span. Cardiac enlargement can result from aorticvalve deficiency.
Case #1 Morquio’s This young boy was normal at birth but developed spinalshortening at age 2 yrs and keratin sulfate was noted in urine
SED deformity with LD platyspondyly, horizontal paddle ribs, wine shaped pelvic inlet and coxa varum hip defects
Case #2 Morquio’sTypical epiphyseal deformities with knocked knees in Morquio’s
Case #3 Morquio’s Age 7 8 yrs 18 yrsSevere coxa varum epiphyseal deformity over 11 yrs of growth
Diastrophic Dwarfism (Twisted or Crooked Dwarf) Diastrophic dwarfs are similar to Morquio’s syndrome as far asthe spondyloepiphyseal deformity seen radiologicially but withan additional collagen deficiency of the entire musculoskeletelsystem resulting in severe ligamentous laxity leading to dis-located joints, kyphoscoliosis and resistant club foot deformity.the limbs are shortened because of retarded epiphysealossification centers that are deformed and flatened with growth.The thumbs and great toes are deformed and held in a hitch-hiker’s position. Collagen deficient ears result in a typicalcauliflower deformity. Diastrophic dwarfs are autosomalrecessive.
Case #1 Diastrophic DwarfismYoung boy with SED deformity similar to Morquio’s but with severe major joint dislocation and club feet
Plataspondyly of cervical spine, mid dorsal scoliosis and dislocated hips
Normal appearing head and face except for the cauliflower ear
Dislocated elbow, thumb, & knee withshort long bones 2nd to epiphyseal hypoplasia
Campnodactyly offingers & hitch-hiker’s deformity of thumbsResistant club feet and short toes
Dysplasia Epiphysealis Hemimelica Tarsal Epiphyseal Aclasia (Trevor’s Disease) Trevor’s disease is a rare epiphyseal dysplasia that results inovergrowth of the epiphyseal cartilage in young children seenusually in the lower extremity and on the medial side in malesthree times more common then females.The talus is commonlyinvolved resulting in the term tarsal epiphyseal aclasia. It affectsone side of the body and is rare in the upper extremity. Multiplebones are involved in a single extremity in 65% of cases. Radio-graphically the epiphyseal overgrowth takes on the appearanceof an epiphyseal osteochondroma except for the dystrophiccalcification seen in the cartilagenous cap not seen in a truemeataphyseal osteochondroma. If the diagnosis is establishedearly in childhood the excess hypertrophic epiphyseal cartilagecan be shaved down to match the opposite side of the sameepiphyses before the cartilage converts to subchondral bone.
Case #1 Trevor’s Disease Knee6 yr male with progressivevalgus deformity of kneewith enlarged medial femoralcondyle with dystrophiccalcification treated withcartilage shaving and resultsseen 5 yrs later & no valgus
Case #2 Trevor’s of Hip & Knee 20 mo female with varus knee 2nd to Trevor’s of knee & hip
Case #3 Tarsal Epiphyseal Aclasia Teen aged boy with pseudo osteochondroma medial malleolus resected and surgical specimen seen to your right
Case #4 Tarsal Epiphyseal Aclasia4 yr old male with none tender lump posterior lateral to ankle thought to be an osteochondroma
Case #5 Tarsal Epiphyseal Aclasia6 yr male with progressive painless enlargement and stiffness of ankle and subtalar joint for 2 yrs
Achondroplasia The achondroplastic dwarf is a common autosomal dominientfamilial condition resulting from a deficiency of central inter-sticial embryonic cartilage of the growth plate with severeshortening of the limbs especially at their proximal ends(rhizomelic). The epiphyses are normal and the peripheralappositional portion of the intersticial cartilage grows laterallyas a collar around the epiphyseal ossification center creating aball-in-socket appearance on x-ray examination. Hypoplasia atthe base of the skull results in a low grade hydrocephali butrarely results in mental retardation. Hypoplasia of the middlethird of the facial bones results in a depressed nasion. The spineis normal except for a mild lumbo-dorsal kyphosis and a spinalstenosis in the lumbosacral area that can result in cauda equinacompression at a young adult age. The major difference betweenthe severe epiphyseal dysplasitic dwarfs (pseudo achondro-plastic) and achondroplastic dwarfs is that achondroplastic
dwarfs have strong but short long bones with normal epiphysesthat result in normal joint surfaces that do not develop earlyosteoarthritis as we see in the epiphyseal dysplastic dwarfs.
Case #1 AchondroplasiaYoung achondroplastic boy with mild hydrocephali, a flat chest,rhizomelic short limbs, kyphotic L-2 vertebral body & short ribs
Short strong fingers & classic trident handX-ray of pelvis shows thechampagne glass defect withsquarred off iliac crests.Note short femur with strongcortical bone and normalepiphyses
Case #2 Achondroplasia Rhizomelic short limbs and normal appearing trunk
Stenosis of LS vertebral canal resulting in cauda equina syndromeNormal skull compared to thatof an achondroblastic withsevere stenosis of the foramen magnum
Hypochondroplasia Hypochondroplasia is an autosomal dominant disorder thatbecomes evident later in childhood compared to achondroplasiathat is dwarfted at birth. The head and face appear normal butspinal stenosis is seen in the lumbosacral spine that can causeneurologic problems requiring surgery. Mild rhizomelic short-ening of long bones results in an average adult height of 4’8”.
HypochondroplasiaCase #1 Young adult male with mild rhizomelic shortening of the extremities and stenosis of the LS spine
Thanatophoric Dwarfism (death bearing dwarf) Thanatophoric dwarfism is a very severe variant of achondro-plasia which is usually a dominant new mutation. These dwarfsare frequently still born because of severe hydrocephali resultingin brain damage at birth. Or if they survive birth they frequentlydie soon after because of severe shortening of the ribs resultingin fatal respiratory problems.
Case #1 Thanatophoric Dwarf Still born infant with short limbs, hydrocephali and short ribs
X-ray of short upper extremities and short ribsX-ray of pelvis and short lower extremities
Macrosection of entire femur obtained at autopsy
Achondrogenesis Achondrogenesis is another very severe variant of achondro-plasia which is autosomal recessive and frequently are still bornor die shortly there after. The limbs are very short with severehypoplasia of the hand and foot bones. There is a generalizededema of the entire body resulting in the term “monster child”.
Case #1 Achondrogenesis Still born infant with short limbs, deficient bone in hands & feet, skull and ribs plus generalized body edema