Craniometaphyseal dysplasia (CMD) is characterized by metaphyseal dysplasia with sclerosis and hyperostosis of cranial bones. CMD is usually autosomal dominant, although autosomal recessive inheritance has been reported. The long bones have broadened metaphyses and develop an ''Erlenmeyer flask'' appearance. Hyperostosis of calvarial and facial bones leads to nasal obstruction, compression of the cranial nerves, and hypertelorism. Much of the disability associated with CMD is due to facial nerve palsy and hearing loss secondary to nerve compression. Linkage between autosomal dominant CMD and chromosome 5p15.2-p14.1 has been established in three kindreds (Chandler et al., 2001; Nurnberg et al., 1997). Studies of the positional candidate gene, ANKH, have revealed several missense mutations, deletions and insertions (Nurnberg et al., 2001; Reichenberger et al., 2001). ANKH encodes a transmembrane protein (ANKH) expressed in osteoblasts that transports inorganic pyrophosphate (PPi) (Figure 27.1). The functional significance of the ANKH mutations found in CMD has yet to be established.
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