Abnormal skeletal growth in Kniest dysplasia caused by type II collagen mutations.

Two unrelated patients with Kniest dysplasia had the same substitution of a CG dinucleotide in exon 12 of the COL2A1 gene that resulted in alternative splicing and interruption of the triple helix of a1(II) chains of Type II collagen. In early childhood, they shared the typical clinical and radiographic features of Kniest dysplasia. However, one child was affected more severely from birth and showed progressive severe disruption of growth plates with retarded longitudinal growth, deformities from asymmetric growth, and widespread sclerosis of the epiphyses. Both children had clinical and radiographic signs of degenerative arthritis of many joints by 11 years of age. The phenotypes in these children highlight the importance of exon 12 mutations of COL2A1 in the pathogenesis of Kniest dysplasia.