New brittle bone disorder: Report of a family with six affected individuals

We report on a family in which four females and two males in three generati ons had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the dis order comprised dolichocephaly with frontal bossing, hypoplasia of the midf ace, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondy lar modification and iliac hypoplasia were other hallmarks that were recogn ized in childhood. The proband, a 19-year-old male, was most severely affec ted with multiple wormian bones in the calvaria, repetitive fractures, intr actable bowing of the legs and forearms, and pseudofractures of the long bo nes with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were muc h less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or a n X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and dis organized chondro-osseous junction, which implied that the disorder involve d both intramembranous and enchondral ossifications. (C) 1999 Wiley-Liss, I nc.