Metatropic dwarfism. Uncoupling of endochondral and perichondral growth

Metatropic dwarfism is a rare heritable skeletal dysplasia that is thought to result from a defect in endochondral ossification. Histological studies have been few and have yielded inconsistent findings. In addition, no investigator has commented on the structure and function of the perichondral portion of the growth plate in patients who have metatropic dysplasia. To further characterize this disturbance, histological studies were carried out on autopsy specimens from the proximal part of the femur and the iliac crest of a patient who had this disorder. The major findings were: the absence of formation of normal primary spongiosa in the metaphysis; the presence of a thin seal of bone at the chondro-osseous junction, with abnormal metaphyseal vascular invasion and arrest of endochondral growth; and normal-appearing perichondral ring structures with persistence of circumferential growth. These findings suggest an uncoupling of endochondral and perichondral growth and offer an explanation for the dumbbell-shaped morphological structure of the osseous metaphysis that is seen in patients who have metatropic dysplasia. Other observations included prominence of the cartilaginous canals and vascular channels in the reserve zone; clumping of chondrocytes with enhanced staining of the pericellular matrix in the proliferative zone; a decreased ratio of cells to matrix in the hypertrophic zone, with intracellular metachromatic granules and incomplete evolution of chondrocytes; complete absence of an alcian-blue-positive zone of provisional calcification; and, finally, islands of dysplastic chondrocytes in the metaphysis. These abnormalities suggest that metatropic dysplasia is not simply a disorder of endochondral ossification. There appear to be associated defects in the longitudinal proliferation and maturation of chondrocytes and in the production of normal matrix.