13 Campomelic Dysplasia
Campomelic Dysplasia 611
CMPD, CMD1
Large, dolichocephalic head, small mouth, microg- nathia, bowed femurs and tibias, small chest, protrud- ing abdomen, short hands and feet phalanges, sex re- versal
Frequency: 0.5 per 100,000 births.
Genetics
Autosomal dominant (OMIM 114290), due to muta- tion of the SOX9 (OMIM 211970) gene at 17q24.3–
25.1; predominance of phenotypic females due to sex reversal; previous evidence suggesting autosomal recessive inheritance now discredited.
Clinical Features
• Large head
• Short-limb dwarfism
• Neonatal death usual
• Small, flat face, with ocular hypertelorism
• Short neck
• Depressed nasal root
• Large philtrum, small mouth, cleft palate
• Micrognathia
• Low-set ears
• Small thorax, hypoplastic lungs
• Bowing of tibias, with pretibial cutaneous dim- pling
• Small hands
• Equinovarus foot deformities
• Sex reversal in some XY males
• Hypotonia
• Congenital heart disease
• Hydrocephalus
• Joint contractures
• Early death due to tracheal cartilage hypoplasia
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Fig. 13.1. Patient 1, newborn. Large head, low-set ears, short limbs, with severe bowing of lower limbs, and cutaneous pretibial dimpling. Note also equinovarus deformity of feet and ambiguous external genitalia. (Reprinted, with permis- sion, from Segrè et al. 1978)
Fig. 13.2. Patient 1, newborn. Skull is enlarged, with promi- nence of calvarium relative to skull base and facial bones.
Frontal bones are high and flat, occiput is prominent. (Reprint- ed, with permission, from Segrè et al. 1978)
Differential Diagnosis
• Congenital bowing of the long bones
• Kyphomelic dysplasia
• Stüve-Wiedemann syndrome
Radiographic Features Limbs
• Anterolateral angulation of femurs
• Hypoplasia and anterior angulation of tibias (anterior angulation)
• Absent epiphyses at the knee (95%)
• Hypoplastic fibulas
• Shortness and mild angulation (25°) of upper limbs
• Radial head dislocation
• Short phalanges of hands and feet
• Squared-off appearance of distal phalanges
• Clinodactyly of 5th fingers
• Poor/absent ossification of talus (80%)
• Talipes equinovarus Chest
• Hypoplastic scapulae
• Eleven pairs of ribs, slender ribs
• Small, bell-shaped thorax
• Absent mineralization of sternum
• Clavicles with lateral hooks Spine
• Hypoplastic and poorly ossified cervical vertebrae
• Hypoplastic pedicles of the thoracic spine
• Cervical kyphosis
• Platyspondyly Skull
• Enlarged/elongated skull (small chondrocranium, large neurocranium)
• High flat forehead
• Bulging occiput
• Platybasia, relatively narrow base
• Large anterior fontanels and sutures
• Antegonal notching of mandible
Pelvis
• Narrow and tall iliac wings, with increased acetab- ular angles
• Absent or poorly ossified pubic bones and ala of sacrum
• Widely spaced vertical ischia
• Hip dislocation
Bibliography
Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B.
Sox9 is required for cartilage formation. Nat Genet 1999;
22: 85–9
Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanovic M, Weissenbach J, Mansour S, Young ID, Goodfellow PN, Brook JD, Schafer AJ. Campomelic dyspla- sia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 1994; 372: 525–30
Glass RB, Rosenbaum KM. Acampomelic campomelic dyspla- sia: Further radiographic variations. Am J Med Genet 1997;
69: 29–32
Lynch SA, Gaunt ML, Minford AMB. Campomelic dysplasia:
evidence of autosomal dominant inheritance. J Med Genet 1993; 30: 683–6
Mansour S, Hall CM, Pembrey ME, Young ID. A clinical and ge- netic study of campomelic dysplasia. J Med Genet 1995; 32:
415–20
Segrè A, Beluffi G, Peretti G. Camptomelic syndrome. A rare type of congenital dwarfism associated with skeletal and other abnormalities. Ital J Orthop Traumatol 1978; 4: 237- 52
Campomelic Dysplasia 612
Campomelic Dysplasia 613
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Fig. 13.3 a, b. Patient 1, newborn. Thoracic cage is bell-shaped, with horizontal ribs. Both scapulae are hypoplastic. Clavicles show lateral hooks. (Reprinted, with permission, from Segrè et al. 1978)
a b
Fig. 13.4. Patient 1, newborn. Pelvic configuration is charac- teristic: ilia are narrow and vertically elongated, ischia are short, widely spaced, and vertically oriented, pubic bones are poorly ossified. Also note bilateral hip dislocation and charac- teristic anterolateral angulation of both femurs and tibias.
(Reprinted, with permission, from Segrè et al. 1978)
Fig. 13.5. Patient 1, newborn. Note anterior angulation of both tibias and femurs, hypoplasia of tibias and fibulas, equino- varus deformity of both feet, and unossified talus. (Reprinted, with permission, from Segrè et al. 1978)
