Osteogenesis imperfecta (OI) or "brittle bone disease" is characterized by reduced skeletal mass and bone fragility. OI has served as the paradigm for heritable diseases of connective tissue from which advances in molecular diagnosis, mode of inheritance, and new concepts of therapy have been developed. The hallmark of OI is bone brittleness. All other characteristics (blue sclerae, dentinogenesis imperfecta, skin hyperlaxity, joint hypermobility, reduced stature, long bone deformities) are variable, with heterogeneity even in affected members of the same family. The severity of OI ranges from mild forms with no deformity, near normal stature, and few fractures to forms that are lethal in the perinatal period. In this form of OI, newborns do not survive the perinatal period. Death is caused by extreme fragility of the ribs and pulmonary hypoplasia or by central nervous system malformations or hemorrhage. Bone mineral density is severely decreased, and infants present with multiple intrauterine fractures (including skull, long bones, and vertebrae), beaded ribs, and severe deformity of the long bones.