30 Craniometaphyseal Dysplasia, Dominant Type
CMD, craniometaphyseal dysplasia, Jackson type
Metaphyseal dysplasia, conspicuous involvement of craniofacial bones, signs of cranial nerve impinge- ment
Frequency: Rare (fewer than 100 published cases).
Genetics
Autosomal dominant (OMIM 123000), relatively mild and common compared with the autosomal recessive (OMIM 218400) form, which is possibly heteroge- neous. The autosomal dominant form is caused by mutations of the ANK gene, which has been mapped to chromosome 5p15.2-p14.1. The ANK gene encodes a protein regulating the transmembranous transport of intracellular pyrophosphate into the extracellular matrix. The recessive form has been mapped to 6q21-q22.
Craniometaphyseal Dysplasia, Dominant Type 664
Fig. 30.1. aPatient 1, age 9 years.
b–d Patient 2 b during late child- hood and c, d adulthood. Thick bony wedge over the nose, nasal bridge, and glabella; hyper- telorism; wide nasal bridge; and small triangular nose
a b
d c
Clinical Features
• Characteristic facial abnormality, with a thick bony wedge over the nasal bridge and glabella
• Hypertelorism, wide nasal bridge, chronic rhinitis due to narrow nasal airway
• Facial palsy, cranial nerve compression of nerves II, VII, VIII
• Wide alveolar ridges
• Hearing loss
• Normal intelligence and stature Differential Diagnosis
• Pyle disease (pure metaphyseal dysplasia with little or no craniofacial involvement)
• Camurati-Engelmann disease
• Craniodiaphyseal dysplasia
• Diaphyseal dysplasia
• Frontometaphyseal dysplasia
• Sclerosteosis
Radiographic Features Skull
• Progressive hyperostosis and sclerosis of cranial vault (frontal and occipital portions most in- volved), skull base, and less often, mandible and facial bones
• Dolichocephaly, with sutural sclerosis
• Hypertelorism
• Narrowing of cranial foramina
• Obliteration of nasal cavity, paranasal sinuses and mastoids
• Tooth defects (thick alveolar ridges, malalignment, delayed eruption) Limbs
• Metaphyseal flaring, with club-shaped configura- tion of femurs (milder than the Erlenmeyer defor- mity of Pyle disease), developing in childhood and adulthood
• Minimal diaphyseal sclerosis (in infancy)
• Undermodeled, short tubular bones, with cortical sclerosis (often confined to distal segments) Chest
• Widened, dense ribs
Craniometaphyseal Dysplasia, Dominant Type 665
C
Fig. 30.2 a, b. Progressive hyperostotic changes involving the calvarium, skull base, and facial bones in a patient 3, age 4 months, in whom evidence of patchy sclerosis of the parietal bones is seen, and b patient 4, an adult. (Reprinted, with per- mission, from Tinschert and Braun 1998)
a
b
Bibliography
Beighton P. Craniometaphyseal dysplasia (CMD), autosomal dominant form. J Med Genet 1995; 32: 370–4
Beighton P, Hamersma H, Horan F. Craniometaphyseal dyspla- sia-variability of expression within a large family. Clin Genet 1979; 15: 252–8
Gorlin RJ, Spranger J, Koszalka MF. Genetic craniotubular bone dysplasias and hyperostoses: a critical analysis. Birth Defects Orig Art Ser 1969; 5: 79–95
Reichenberger E, Tiziani V, Watanabe S, Park L, Ueki Y, Santana C, Baur ST, Shiang R, Grange DK, Beighton P, Gardner J,
Hamersma H, Sellars S, Ramesar R, Lidral AC, Sommer A, Raposo do Amaral CM, Gorlin RJ, Mulliken JB, Olsen BR.
Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.
Am J Hum Genet 2001; 68: 1321–6
Taylor DB, Sprague P. Dominant craniometaphyseal dysplasia – a family study over five generations. Australas Radiol 1989; 33: 84–9
Tinschert S, Braun HS. Craniometaphyseal dysplasia in six generations of a German kindred. Am J Med Genet 1998;
77: 175–81 Craniometaphyseal Dysplasia, Dominant Type
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Fig. 30.3. aPatient 3, age 4 months. Note flaring of the distal femoral metaphyses and diaphyseal sclerosis. Characteristic flaring of the distal femoral metaphyses. b Patient 4 (adult). (Reprinted, with permission, from Tinschert and Braun 1998)
a b
