Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embding technique. Extensive vacuolar changes were observed p-1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.SpeculationThe findings suggest that there may be a defect in the synthesis, structure, or secretion of a major cartilage matrix component (e.g, proteoglycan, collagen) which leads to its accumulation in the chondrocyte rough endoplasmic reticulum. Both cellular and matrix degeneration subsequently occur either due to a toxic effect of this material or to the absence of the normal molecule.