We performed histochemical, immunohistochemical, electron-microscopic, and microchemical studies on cartilage growth plates from sixty-eight patients with nineteen different forms of human osteochondrodysplasia. Cartilage biopsies were obtained during orthopaedic procedures. Postmortem specimens were obtained within a short time after death. The combined morphological and biochemical studies revealed specific abnormalities suggestive of a particular biochemical defect in several chondrodysplasias. In pseudoachondroplasia, non-collagenous protein accumulated in the rough endoplasmic reticulum of chondrocytes and a proteoglycan species that normally is present in the extracellular matrix was not detected by gel electrophoresis. The accumulated material was stained with antibodies against the core protein of proteoglycan. This strongly suggested that in this syndrome an abnormal core protein of a proteoglycan species is not properly transferred to the Golgi system. In Kniest syndrome, intracytoplasmic accumulation of metachromatic material, dilatation of rough endoplasmic reticulum, and an abnormal gel-electrophoretic pattern of cartilage proteoglycans suggested an abnormality of cartilage proteoglycan metabolism. Abnormalities that probably are related to degradative lysosomal processes of proteoglycans in chondrocytes were found in spondylometaphyseal dysplasia of the Kozlowski type. An abnormal organization of type-II collagen was found in fibrochondrogenesis. In diastrophic dysplasia, an abnormal organization of collagen was found in areas of interterritorial matrix and around many degenerated cells, but also in the lacunae of cells without ultrastructural signs of degeneration. The segment-long-spacing form of collagen prepared from cartilage of three patients with diastrophic dysplasia showed an abnormal cross-striation pattern in a portion between bands 42 and 45, corresponding to the position of the alpha 1(II) cyanogen-bromide-derived 10,5 peptide. This suggested that in this syndrome there is a structural alteration of the type-II collagen molecule. There was an accumulation of intracellular lipid in pyknodysostosis and in hypochondrogenesis, and of glycoproteins in several atypical cases of spondyloepiphyseal dysplasia. In a pair of twins with an atypical form of spondyloepiphyseal dysplasia, the presence of many multinucleated chondrocytes suggested a primary impairment of cell division.
Clinical relevance: A knowledge of the pathogenic mechanisms in osteochondrodysplasias might improve the classification; aid in diagnosis, prognosis, and genetic counseling; and contribute to the understanding of normal endochondral growth.(ABSTRACT TRUNCATED AT 400 WORDS)