Chapter 156 - Osteogenesis Imperfecta (and Other Disorders of Bone Matrix)

Abstract

While reduced bone density (osteopenia = lit . less bone) is encountered in hundreds of dysplasias and syndromes that affect the skeleton, bone fragility, particularly a predisposition to fractures before birth or in the first years of life, is only found in a small group of disorders. The major disorders with bone fragility include the osteogenesis imperfecta (OI) syndromes, hypophosphatasia, and several other inborn errors of metabolism. While the majority of cases of OI in European populations appear to be mutations that result in quantitative and/or qualitative defects in type I collagen genes, mutations in at least nine other genes have been demonstrated to result in various forms of OI, and these are numerically the most common causes in Africa, the Middle East and southern Asia. The current approved nosology for OI groups them into five broad clinical genetic syndrome groups, each of which is genetically heterogenous. These are non-deforming OI with blue sclerae, common variable OI with normal sclerae, OI with calcification in interosseous membranes, progressively deforming OI, and perinatally lethal OI. In addition, there are a number of rare special syndromes such as the Bruck syndromes and syndromes of brittle bones with various types of eye impairment.