Pathophysiology
Clinical meaning
Osteogenesis imperfecta (OI), commonly known as brittle bone disease, is a group of genetic connective tissue disorders caused by defects in the synthesis, structure, or processing of type I collagen. Type I collagen is the most abundant protein in the human body and is a major structural component of bone, skin, tendons, ligaments, sclera of the eyes, dentin of the teeth, and blood vessel walls. Because type I collagen is so widely distributed, OI affects multiple organ systems, although its most prominent clinical feature is bone fragility with recurrent fractures. The molecular basis of OI involves mutations in one of several genes, most commonly COL1A1 and COL1A2, which encode the alpha-1 and alpha-2 chains of type I procollagen, respectively. These mutations produce either quantitatively deficient collagen (less collagen of normal quality) or qualitatively abnormal collagen (normal amounts of structurally defective collagen). The Sillence classification system divides OI into four main types based on clinical severity. Type I (mild, most common, accounting for approximately 50 percent of cases) produces collagen of normal quality but in reduced quantity; patients have blue sclera,...