Metaphyseal anadysplasia: Evidence of genetic heterogeneity

We report on two unrelated children, a girl and a boy, with regressive metaphyseal dysplasia. Both children had bow legs and a transient growth decline in early childhood. Metaphyseal modifications of the long bones in the children were most conspicuous at an early age and then subsided by age 2 to 3 years. The father of the boy may have had the same disorder, because he was shorter than his sibs and showed mild modifications of the vertebral end plates with mild narrowing of the interpediculate distance of the lumbar spine. The evolution of the metaphyseal dysplasia in the children closely resembled that of metaphyseal anadysplasia (MAD), which is X-linked recessive in inheritance. By contrast, the occurrence of an isolated, affected girl and possible father-to-son transmission reported here were consistent with autosomal dominant transmission, suggesting heterogeneity of MAD. Molecular studies of the type X collagen gene in the boy did not demonstrate any disease-causing mutation. Am. J. Med. Genet. 82:43–48, 1999. © 1999 Wiley-Liss, Inc.