SKELETAL DYSPLASIAS WITH GRACILE BONES - 3 NEW CASES, INCLUDING 2 OFFSPRING OF A MOTHER WITH A DWARFING CONDITION

We describe 3 new cases of a rare form of dwarfism (so-called ''lethal skeletal dysplasia with gracile bones'' or ''osteocraniostenosis''), a condition characterized by thin, brittle bones and death in late ges tation or early neonatal life, The first was a 37-week gestation femal e who died at delivery, She had facial anomalies and positional abnorm alities of the hands and feet. The others were male stillborn sibs, wh o died in utero in the third trimester, Their mother had an undiagnose d dwarfing condition associated with body asymmetry, microcephaly, and unusual facial appearance, Both fetuses were documented by ultrasound to have short limbs and probable long bone fractures late in the seco nd trimester. At autopsy, one fetus had no spleen and the other a hypo plastic spleen, Radiographically, all three cases had very thin diaphy ses, diaphyseal fractures, and thin ribs and clavicles, In contrast to the first case who had a normally mineralized calvaria, the sibs had grossly deficient calvarial mineralization, Microscopically, endochond ral ossification was qualitatively normal but quantitatively deficient in all three cases, The long bones, especially those of the sibs, lac ked the well-defined outer cortex in the mid-shaft; normally seen by t he third trimester, This failure of organization into the cortex and m edulla suggests a failure of bone remodelling, Given the variable pres entation in these cases, ''lethal skeletal dysplasia with gracile bone s'' is probably a heterogeneous disorder, The recurrence in one family suggests that the mother has somatic/germline mosaicism of a lethal g ene, expressed clinically as growth failure and asymmetry. (C) 1998 Wi ley-Liss, Inc.