Kniest Dysplasia: Clinical, Pathologic, and Molecular Findings in a Severely Affected Patient–And Review of the Literature

Abstract

Kniest dysplasia is a chondrodysplasia characterized by disproportionate dwarfism and facial dysmorphic features. Enchondral ossification of hyaline cartilage is impaired, and histologic examination of cartilage shows an abnormal structure (“Swiss cheese” pattern). Dominant mutations within the gene encoding for collagen II (COL2A1), the major cartilage matrix protein, have been identified as the unifying genetic defect. Our paper describes the clinical, radiologic, pathologic, and molecular features of a patient with severe Kniest dysplasia carrying a novel splice site mutation at position + 1 of intron 22 of the COL2A1 gene with presumed skipping of exon 22. We compare our findings with all published Kniest patients with identified COL2A1 gene mutations. There is a strong association between collagen II chain length variation and Kniest dysplasia (as opposed to amino acid substitutions), suggesting a distinct pathophysiologic mechanism leading to the characteristic “hypertrophy” of cartilage; the nature of this mechanism is discussed.

Key Words:

• cartilage
• collagen II
• COL2A1
• dwarfism
• Kniest dysplasia
• osteochondrodysplasia