Genetic Disorders of Bone and Connective Tissue (Skeletal Dysplasias)

Abstract

Even single gene mutations may manifest as generalised or local disorders of the skeleton known as skeletal dysplasias or constitutional bone disorders. Patients with these disorders usually have short stature, abnormally shaped bones and often with pathologic fracture. There exist more than 170 variants of skeletal dysplasias, and the most frequent are osteogenesis imperfecta, osteopetrosis, osteopoikilosis and achondroplasia. Recent progress has led to the identification of many gene mutations that cause skeletal dysplasia, for example, osteogenesis imperfecta, an autosomal dominant condition caused by defects in type I collagen. Subsequent biochemical and molecular studies revealed both quantitative and structural defects in either of the two chains that form the type I collagen heterotrimer. Many dysplasias once thought to be different disorders are now known to be variants of a different expression of the same gene defect. New genetic, biochemical and molecular informations will be the basis of a future classification system of constitutional skeletal dysplasias.