Kniest dysplasia is characterized by an apparent abnormal processing of the C-propeptide of type II cartilage collagen resulting in imperfect fibril assembly.

Epiphyseal and growth plate cartilages from four cases of Kniest dysplasia have been studied. In each case collagen fibril organization appeared abnormal by electron microscopy compared with age-matched normal cartilages: fibrils were much thinner, of irregular shape and did not exhibit the characteristic banding pattern. This was associated with the absence (compared with normal cartilage) of the C-propeptide of type II collagen (chondrocalcin) from the extracellular matrix of epiphyseal cartilages, although it was detected (as in normal cartilages) in the lower hypertrophic zone of the growth plate in association with calcifying cartilage. The C-propeptide was abnormally concentrated in intracellular vacuolar sites in Kniest cartilages and its total content was reduced in all cases but not in all cartilages. Moreover, it was not a part of the procollagen molecule. In contrast, type II collagen alpha-chain size was normal, indicating the formation of a triple helix. Also type II collagen content was normal and it was present in extracellular sites and only occasionally detected intracellularly. These observations suggest that the defect in Kniest dysplasia may result from the secretion of type II procollagen lacking the C-propeptide and abnormal fibril formation, and that the C-propeptide is normally required for fibril formation.