Osteogenesis imperfecta: an expanding panorama of variants

Abstract

Our concept of osteogenesis imperfecta (OI) has expanded considerably in the last decade. Both clinical and genetic studies on the one hand and biochemical studies on the other suggest considerable pathogenetic heterogeneity. Clinically, four broad groups can be distinguished. Two groups are characterized by dominant inheritance of osseous fragility with further heterogeneity determined by the presence or absence of opalescent dentin in families. A further two groups are characterized by autosomal recessive inheritance of severe or extreme bone fragility. An X-linked variety of OI also seems likely and a number of unique variants have been reported. These clinically defined groups are likely to represent classes of molecular defects. While there is evidence for disturbed regulation of collagen synthesis in some groups, it is possible that the primary defect in some cases may be in glycosaminoglycan/proteoglycan metabolism or even in skeletal cell metabolism leading to defective skeletal organization. Insight into the pathogenesis of these disorders will eventually permit specific therapy, prenatal diagnosis and more accurate genetic counseling for the osteogenesis imperfecta syndromes.