648 Cleidocranial Dysplasia

25 Cleidocranial Dysplasia

Cleidocranial dysostosis, CCD Radiographic Features Skull Persistently open skull sutures, brachycephaly, frontal/ • Brachycephaly, increased biparietal diameter, fron- parietal bossing, depressed nasal bridge, dental anom- tal bossing, bulging calvaria alies, increased shoulder movement/narrow shoulders • Delayed skull ossification, persistently opened su- tures (metopic, posterior occipital synchondrosis) Frequency: 0.5 per 100,000 births. and fontanels (until adulthood) • Multiple wormian bones Genetics • Hypoplasia of facial bones Autosomal dominant (OMIM 119600); the disease • Broad mandible, prognathism gene, CBFA1, which is essential for osteoblast differ- • Delay in deciduous and permanent dentition entiation, maps to 6p21. • Teeth irregularly placed, dental caries • High-arched palate Clinical Features • Underdeveloped sinuses and mastoids • Moderately short stature • Structural ossicular chain abnormalities • Large head, prominent frontal and parietal bones Chest (‘Arnold head’), wide sutures • Partial, less frequently total, aplasia of clavicles, • Midfacial hypoplasia, facial palsy mostly bilateral; clavicles most commonly defec- • Hypertelorism, broad nasal bridge tive in lateral and middle thirds; lack of fusion of • Delayed teeth eruption, persistence of primary lateral and medial segments of clavicles with a teeth, supernumerary teeth central gap • Drooping and hypermobile shoulders, hypoplas- • Narrow thorax, short ribs tic/aplastic clavicles • Small and deformed scapulae • Narrow thorax, respiratory distress • Eleven pairs of ribs • Brachydactyly • Pectus excavatum, under-/unossified sternum • Joint laxity Pelvis • Absence or delayed ossification of pubic bones (in Differential Diagnosis infancy) • Pyknodysostosis • Hypoplasia and anterior rotation of iliac wings, • Yunis-Varon syndrome hypoplastic acetabulum • Mandibuloacral dysplasia • Hip dislocation • Cleidorhizomelic dysplasia • Wide pubic symphysis (in adults), sacroiliac junc- • Crane-Haise syndrome tion, and Y-cartilage of the acetabulum • Parietal foramina with cleidocranial dysplasia • Cephalopelvic disproportion • Craniomandibular dermosynostosis • Pelvic-shoulder dysplasia • Scapuloiliac dysostosis Cleidocranial Dysplasia 649

Fig. 25.1 a,b. Patient 1, age 4 years. Note frontal and parietal bossing, ocular hypertelorism, and abnor- mal mobility of the shoulders. Note also funnel-shaped chest in b

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Hands and Feet Bibliography • Brachydactyly • Multiple, large pseudoepiphyses of metacarpals Chitayat D, Hodgkinson KA, Azouz EM. Intrafamilial variabil- and metatarsals ity in cleidocranial dysplasia: a three generation family.Am • J Med Genet 1992; 42: 298–303 Relatively long 2nd and 5th metacarpals Jackson WPU. Osteo-dental-dysplasia (cleido-cranial dysosto- • Thin metacarpals and metatarsals sis). The “Arnold head.”Acta Med Scand 1951; 139: 292–307 • Short, dysplastic middle phalanx of the 5th finger Jarvis JL, Keats TE. Cleidocranial dysostosis. A review of 40 • Small, distally tapering terminal phalanges new cases. Am J Roentgenol Radium Ther Nucl Med 1974; • Cone-shaped epiphyses of phalanges of fingers 121: 5–16 Jensen BL, Kreiborg S. Development of the skull in infants with and toes cleidocranial dysplasia. J Craniofac Genet Dev Biol 1993; Extremities 13: 89–97 • Undermodeling of long bones, narrow shafts of Lee B,Thirunavukkarasu K,Zhou L,Pastore L,Baldini A,Hecht the tubular bones J, Geoffroy V,Ducy P,Karsenty G. Missense mutations abol- • Coxa valga or, less frequently, coxa vara ishing DNA binding of the osteoblast-specific transcription • factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet Deformed femoral head and neck 1997; 16: 307–10 • Shortness or absence of fibulae Mundlos S. Cleidocranial dysplasia: clinical and molecular ge- Spine netics. J Med Genet 1999; 36: 177–82 • Posterior wedging of thoracic vertebrae Mundlos S, Mulliken JB, Abramson DL, Warman ML, Knoll • Persistence of synchondrosis between vertebral JHM, Olsen BR. Genetic mapping of cleidocranial dysplasia and evidence of a microdeletion in one family. Hum Mol bodies and neural arches Genet 1995; 4: 71–5 • Spina bifida Reed MH, Houston CS. Abnormal ossification of the hyoid • Kyphoscoliosis bone in cleidocranial dysplasia. Can Assoc Radiol J 1993; • Lumbar spondylolysis 44: 277–9 Generalized Bone Defects Seow WK, Hertzberg J. Dental development and molar root • length in children with cleidocranial dysplasia. Pediatr Delayed bone age Dent 1995; 17: 101–5 650 Cleidocranial Dysplasia

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Fig. 25.2. a, b Patient 1,age 4 years; c patient 2, age 12 years; d, e pa- tient 3, an adult: wormian bones in the cranial sutures, and widely opened anterior fontanel and metopic suture in all patients. The cranial transverse diameter is increased, and the facial bones are relatively hypoplastic. Note also lack of pneumatization of e sinuses and moderate basilar im- pression (e) Cleidocranial Dysplasia 651

Fig. 25.3. a Patient 1, age 4 years; right clavicle is missing, and left clavicle is markedly hypoplastic. Also observe lack of fusion of the neural arches of upper thoracic vertebrae, bell-shaped thorax, and dysplastic, anteverted sca- pulae. b Patient 4, adolescent; note central gap in right clavicle and mildly hypoplasia of left clav- icle, which has a straight course. C c Patient 3, adult; bilateral lack of osseous fusion between lateral and the medial two-thirds of the clavicles.Also note severe thoracic scoliosis

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c 652 Cleidocranial Dysplasia

Fig. 25.4. a Patient 1, age 4 years. Note narrowing of ilia, with small acetabular angles, unossified pu- bic bones, wide sacroiliac junc- tions, wide open Y cartilages, and narrow sacrosciatic notches. b Patient 3, adult. Iliac wings are somewhat narrowed in their transverse diameter, sacroiliac junctions are wide, and pelvic in- let is small.Note incomplete ossifi- cation of pubic bones, short and valgus femoral necks, and per- sistent physeal lines of proximal femurs

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Fig. 25.5. Patient 3, adult. Note narrowing of midshaft of tibia and undermodeling of tibia and fibula

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Fig. 25.6. a, b Patient 1, age 4 years. Note hypoplastic, distally pseudoepiphysis will result in relative elongation of the tapering distal phalanges, hypoplastic middle phalanges of metacarpal. Observe markedly retarded carpal bone ossifica- 2nd and 5th fingers, multiple cone-shaped epiphyses, and tion (corresponding to a chronological age of 1 year and pseudo-epiphysis at base of 2nd metacarpal. Fusion of the 6 months according to Greulich and Pyle)