25 Cleidocranial Dysplasia
Cleidocranial dysostosis, CCD
Persistently open skull sutures, brachycephaly, frontal/
parietal bossing, depressed nasal bridge, dental anom- alies, increased shoulder movement/narrow shoulders Frequency: 0.5 per 100,000 births.
Genetics
Autosomal dominant (OMIM 119600); the disease gene, CBFA1, which is essential for osteoblast differ- entiation, maps to 6p21.
Clinical Features
• Moderately short stature
• Large head, prominent frontal and parietal bones (‘Arnold head’), wide sutures
• Midfacial hypoplasia, facial palsy
• Hypertelorism, broad nasal bridge
• Delayed teeth eruption, persistence of primary teeth, supernumerary teeth
• Drooping and hypermobile shoulders, hypoplas- tic/aplastic clavicles
• Narrow thorax, respiratory distress
• Brachydactyly
• Joint laxity
Differential Diagnosis
• Pyknodysostosis
• Yunis-Varon syndrome
• Mandibuloacral dysplasia
• Cleidorhizomelic dysplasia
• Crane-Haise syndrome
• Parietal foramina with cleidocranial dysplasia
• Craniomandibular dermosynostosis
• Pelvic-shoulder dysplasia
• Scapuloiliac dysostosis
Radiographic Features Skull
• Brachycephaly, increased biparietal diameter, fron- tal bossing, bulging calvaria
• Delayed skull ossification, persistently opened su- tures (metopic, posterior occipital synchondrosis) and fontanels (until adulthood)
• Multiple wormian bones
• Hypoplasia of facial bones
• Broad mandible, prognathism
• Delay in deciduous and permanent dentition
• Teeth irregularly placed, dental caries
• High-arched palate
• Underdeveloped sinuses and mastoids
• Structural ossicular chain abnormalities Chest
• Partial, less frequently total, aplasia of clavicles, mostly bilateral; clavicles most commonly defec- tive in lateral and middle thirds; lack of fusion of lateral and medial segments of clavicles with a central gap
• Narrow thorax, short ribs
• Small and deformed scapulae
• Eleven pairs of ribs
• Pectus excavatum, under-/unossified sternum Pelvis
• Absence or delayed ossification of pubic bones (in infancy)
• Hypoplasia and anterior rotation of iliac wings, hypoplastic acetabulum
• Hip dislocation
• Wide pubic symphysis (in adults), sacroiliac junc- tion, and Y-cartilage of the acetabulum
• Cephalopelvic disproportion
Hands and Feet
• Brachydactyly
• Multiple, large pseudoepiphyses of metacarpals and metatarsals
• Relatively long 2nd and 5th metacarpals
• Thin metacarpals and metatarsals
• Short, dysplastic middle phalanx of the 5th finger
• Small, distally tapering terminal phalanges
• Cone-shaped epiphyses of phalanges of fingers and toes
Extremities
• Undermodeling of long bones, narrow shafts of the tubular bones
• Coxa valga or, less frequently, coxa vara
• Deformed femoral head and neck
• Shortness or absence of fibulae Spine
• Posterior wedging of thoracic vertebrae
• Persistence of synchondrosis between vertebral bodies and neural arches
• Spina bifida
• Kyphoscoliosis
• Lumbar spondylolysis Generalized Bone Defects
• Delayed bone age
Bibliography
Chitayat D, Hodgkinson KA, Azouz EM. Intrafamilial variabil- ity in cleidocranial dysplasia: a three generation family. Am J Med Genet 1992; 42: 298–303
Jackson WPU. Osteo-dental-dysplasia (cleido-cranial dysosto- sis). The “Arnold head.” Acta Med Scand 1951; 139: 292–307 Jarvis JL, Keats TE. Cleidocranial dysostosis. A review of 40 new cases. Am J Roentgenol Radium Ther Nucl Med 1974;
121: 5–16
Jensen BL, Kreiborg S. Development of the skull in infants with cleidocranial dysplasia. J Craniofac Genet Dev Biol 1993;
13: 89–97
Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G. Missense mutations abol- ishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet 1997; 16: 307–10
Mundlos S. Cleidocranial dysplasia: clinical and molecular ge- netics. J Med Genet 1999; 36: 177–82
Mundlos S, Mulliken JB, Abramson DL, Warman ML, Knoll JHM, Olsen BR. Genetic mapping of cleidocranial dysplasia and evidence of a microdeletion in one family. Hum Mol Genet 1995; 4: 71–5
Reed MH, Houston CS. Abnormal ossification of the hyoid bone in cleidocranial dysplasia. Can Assoc Radiol J 1993;
44: 277–9
Seow WK, Hertzberg J. Dental development and molar root length in children with cleidocranial dysplasia. Pediatr Dent 1995; 17: 101–5
a b
a b
c
e
d
Fig. 25.2. a, bPatient 1, age 4 years;
cpatient 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 sinuses and moderate basilar im- pression (e)
clavicles. Also note severe thoracic scoliosis
a
b
c
Fig. 25.4. aPatient 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
a
b
Fig. 25.6. a, bPatient 1, age 4 years. Note hypoplastic, distally tapering distal phalanges, hypoplastic middle phalanges of 2nd and 5th fingers, multiple cone-shaped epiphyses, and pseudo-epiphysis at base of 2nd metacarpal. Fusion of the
pseudoepiphysis will result in relative elongation of the metacarpal. Observe markedly retarded carpal bone ossifica- tion (corresponding to a chronological age of 1 year and 6 months according to Greulich and Pyle)
a b
