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.