35 Diastrophic Dysplasia
Diastrophic Dysplasia 679
Short-limb dwarfism, clubbed hands/feet, progressive scoliosis, malformed and calcified pinnae, hitchhiker thumb
Frequency: 1 in 500,000 live births; 1 in 30,000 live births in Finland.
Genetics
Autosomal recessive (OMIM 222600); the disease- gene, SLC26A2, a sulfate transporter, has been mapped to 5q32–33.1. Allelic to multiple epiphyseal dysplasia (MED4, OMIM 226900).
Clinical Features
• Short-limb dwarfism, identifiable at birth
• Normal head, round face, narrow nasal bridge
• Hypertrophic auricular cartilage, cystic lesions (‘cauliflower’ ears) that resolve within 1 month, leaving an ossified pinna
• Cleft palate
• Micrognathia
• Respiratory obstruction in the newborn (may be fatal)
• Ulnar deviation of hand,‘hitchhiker’thumbs,sym- phalangism, brachydactyly
• Abnormal gait
• Flexion contracture or subluxation or dislocation of hips and knees
• Club feet
• Progressive scoliosis and kyphosis, risk of cord compression
Differential Diagnosis
• Atelosteogenesis, type 1, 2, and 3
• Pseudodiastrophic dysplasia
• Arthrogryposis syndromes
Radiographic Features Extremities
• Short limbs, mostly mesomelic
• Metaphyseal widening, progressive epiphyseal ab- normalities (flattening, fragmentation and invagi- nation)
• Delayed appearance of capital femoral epiphyses
• Underossified lateral portions of distal femoral epiphyses
• Short and broad proximal femora
• Radial head subluxation Hands and Feet
• Irregularly short tubular bones, with metaphyseal flaring and epiphyseal flattening
• Ovoid 1st metacarpal and metatarsal, with proxi- mally located thumb and toe (until late child- hood)
• Delta-shaped phalanges
• Symphalangism of proximal interphalangeal joints
• Severe talipes equinovarus
• Deformed tarsal and carpal bones
• Advanced carpal ossification centers Spine
• Progressive kyphoscoliosis
• Progressive cervical kyphosis, with atlas subluxa- tion and spinal cord compression
• Clefting of posterior processes of cervical and sacral vertebrae
• Platyspondyly and hypoplasia of cervical verte- brae
• Narrowing of the interpediculate distance at lum- bar spine
Chest
• Premature costochondral calcification
• Clavicles with lateral hooks Skull
• Intracranial calcification Generalized Bone Defects
• Multiple joint subluxations or dislocations (hip, patella, elbow, cranio-cervical junction)
D
Fig. 35.2. aPatient 2, newborn. Note marked kyphosis of the cervical spine, cervical platyspondyly, and atlas subluxation.
bPatient 3, age 6 years. There is striking odontoid hypoplasia in this child. On occasion, odontoid hyperplasia can be encountered in diastrophic dysplasia
a
b
Fig. 35.1. Patient 1, 2 years and 6 months. Short-limb dwarfism, normal head, flat face, short neck, hitch-hiker thumbs, thoracic gibbus, clubfeet, and restricted joint movements. (Reprinted, with permission, from Mastroiacovo et al. 1990)
Bibliography
Hall BD. Diastrophic dysplasia: extreme variability within a sibship. Am J Med Genet 1996; 63: 28–33
Hastbacka J, de la Chapelle A, Mahtani MM, Clines G, Reeve- Daly MP, Daly M, Hamilton BA, Kisumi K, Trivedi B, Weaver A, Coloma A, Lowett M, Buckler A, Koitila I, Lancer ES. The diastrophic dysplasia gene encodes a novel sulfate trans- porter: positional cloning by fine-structure linkage dise- quilibrium mapping. Cell 1994; 78: 1073–87
Horton WA, Rimoin DL, Lachman RS, Skovby F, Hollister DW, Scott CI, Hall JG. The phenotypic variability of diastrophic dysplasia. J Pediatr 1978; 93: 609–13
Lamy M, Maroteaux P. Le nanisme diastrophique. Presse Med 1960; 68: 1977–80
Langer LO. Diastrophic dwarfism in early infancy. AJR Am J Roentgenol 1965; 93: 399–404
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Rossi A, van der Harten HS, Beemer FA, Kleijer WS, Gitzel- mann R, Steinmann B, Superti-Furga A. Phenotypic and genotypic overlap between atelosteogenesis type 2 and di- astrophic dysplasia. Hum Genet 1996; 98: 657–61
Taybi H. Diastrophic dwarfism. Radiology 1963; 80: 1–10 Walker BA, Scott CI, Hall JG, Murdoch JL, McKusick VA. Dias-
trophic dwarfism. Medicine 1972; 51: 41–60
Diastrophic Dysplasia 681
D
Fig. 35.3. aPatient 3, 6 years. b Patient 4, 11 years.
Note clefting of the posterior elements of the cer- vical vertebrae, mild thoracolumbar scoliosis, and narrowing of the interpediculate distance from the upper to the lower lumbar spine
a b
Fig. 35.4. aPatient 3, age 6 years.
b Patient 4, age 11 years. The fe- murs are proximally deficient, with severely underdeveloped capital femoral epiphyses. The proximal femurs appear short, broad, in varus position, and com- pletely dislocated. The ilia are also short and broad, the acetabula are shallow and irregular. The Y-carti- lages are wide open
a
b
Diastrophic Dysplasia 683
D
Fig. 35.5. aPatient 2, newborn. There is shortening of the long bones, with metaphyseal flaring and unossified distal femoral and proximal tibial epiphyses. Note also severe equinovarus deformity of both feet, and unossified pubic rami. b Patient 3,
age 6 years. Note typical epiphyseal flattening. The distal femoral metaphyses, in addition to being widened, show an inverted V-shape configuration, with cone-shaped deformity of the corresponding epiphyses
a b
Fig. 35.6. Patient 3, age 6 years.
The long bones of the upper limb are short with broad metaphyses.
Note flattening of the proximal humeral epiphysis and radial head dislocation
Fig. 35.8. Patient 3, age 6 years. Changes similar to those described in the hands are seen
Fig. 35.7. aPatient 2, newborn. The thumb is proximally locat- ed, in full hyperextension. b Patient 3, age 6 years. There is irregular shortening and deformity of the tubular bones, metaphyseal widening, and epiphyseal flattening and frag- mentation. The 1st metacarpal is ovoid in shape, and proxi-
mally located. The middle phalanges of fingers 2 and 5 are delta-shaped or triangular, with secondary clinodactyly. The epiphyses of the middle phalanges are missing. The carpal bones are variously deformed
a b
