Osteogenesis Imperfecta

This chapter discusses osteogenesis imperfecta (OI), which is a heterogeneous condition characterized by bone fragility. OI is caused by numerous different mutations, with at least 10 different clinical forms, effective symptomatic treatment, and exciting prospects for gene therapy. The prevalence of OI is estimated to be 1 in 15,000-20,000 infants, but misdiagnosis is frequent because it is a heterogeneous condition. OI has served as a paradigm for heritable disease of connective tissue from which advances in molecular diagnosis, mode of inheritance, and new concepts of therapy have been applied. In the vast majority of cases, mutations within the COLIA1 or COLIA2 genes are responsible for the phenotype, although it is now recognized that mutations in other genetic loci can produce a similar clinical outcome. The hallmark of OI is brittle bones. All other characteristics of OI are variable, with heterogeneity even in different members of the same family. Wormian bones are present in the skull in approximately 60% cases, although they can be present in other conditions, such as progeria, cleidocranial dysplasia, Menkes syndrome, and cutis laxa.