Osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a genetically determined disorder of connective tissue characterized by bone fragility. The disease state encompasses a phenotypically and genotypically heterogeneous group of inherited disorders that result from mutations in the genes that code for type I collagen. The disorder is manifest in tissues in which the principal matrix protein is type I collagen (mainly bone, dentin, sclerae, and ligaments). Musculoskeletal manifestations are variable in severity along a continuum ranging from perinatal lethal forms with crumpled bones to moderate forms with deformity and propensity to fracture to clinically silent forms with subtle osteopenia and no deformity. The differential diagnosis includes other entities with multiple fractures, deformities, and osteopenia. Classification is based on the timing of fractures or on multiple clinical, genetic, and radiologic features. Molecular genetic studies have identified more than 150 mutations of the COL1A1 and COL1A2 genes, which encode for type I procollagen. Various systemic treatments have been attempted; however, these interventions have been ineffective or inconclusive or are still experimental. Gene therapy has the potential to increase the synthesis of type I collagen in mild variants and to correct mutations in severe variants, but there are a great number of technical difficulties to overcome. The goals of treatment of OI are to maximize function, minimize deformity and disability, maintain comfort, achieve relative independence in activities of daily living, and enhance social integration. Attainment of these goals requires a team approach to tailor treatment needs to the severity of the disease and the age of the patient. Nonoperative management is the mainstay of orthopaedic treatment, with the goals of preventing and treating fractures and enhancing locomotion. Operative intervention is indicated for recurrent fractures or deformity that impairs function.