Lethal osteosclerotic skeletal dysplasia with intracellular inclusion bodies

We report an apparently previously undescribed form of lethal osteoscleroti c skeletal dysplasia in a 30-week male fetus with micromelic shortness of t he limbs. Radiographic findings at necropsy included increased density in a ll bones, most marked in the skull, mandible, and pubis. The ribs were very short, abnormally modeled, and wide anteriorly. The vertebrae were posteri orls hypoplastic and wedged, particularly in the cervical and lumbar region s. The femora and tibiae were short with wide distal metaphyses, undermodel ed diaphyses, and coxa vara. The humeri, radii, and ulnae were also short a nd undermodeled with proximal and distal flare. Chondro-osseous morphology showed short chondrocyte columns, extension of hypertrophic cells into the metaphysis, and overgrowth of perichondral bone. In the resting cartilage t here were large chondrocytes containing a homogeneous material staining pin k with von Kossa trichrome, gray with toluidine blue, and black with silver methenamine. The cortical bone was lacking and the trabecular bone was hyp ercellular, thick, and coarse. Ultrastructurally, the resting zone chondroc ytes were large and round with condensed chromatin and dilated loops of rou gh endoplasmic reticulum. The radiographic and histopathologic findings in this case are unique and differ from those seen in other reported lethal os teosclerotic skeletal dysplasias. Am. J. Med. Genet. 83:372-377, 1999. (C) 1999 Wiley-Liss, Inc.