Imperfect Osteogenesis. On the purpose of a Type VIII case

Abstract

Classic osteogenesis imperfecta (OI), or “brittle bone disease,” is a connective tissue disorder characterized by susceptibility to bone fractures, blue sclera, and growth failure. The majority (85%) of individuals with OI have autosomal dominant mutations in COL1A1 or COL1A2 that alter the structure or synthesis of type I collagen. Collagen mutations cause a variety of OI phenotypes, from mild to perinatal fatality, described by the Sillence Classification. Autosomal dominant OI has an incidence of 1/15 to 20,000 births, with> 90% of cases resulting from de novo mutations. Mutation “hot spots” in COL1A1 and COL1A2 are associated with independent recurrences of mutations, rather than founder mutations.

Cabral et al. described an autosomal recessive form of OI, which they called OI type VIII, characterized by white sclerae, severe growth deficiency, extreme skeletal mineralization and bulbous metaphyses.

Cabral et al. suggested that defects in LEPRE1 that result in lethal to severe recessive bone dysplasia characterized by white sclerae, severe growth deficiency, extreme skeletal sub-mineralization, and bulbous metaphyses should be classified as type VIII osteogenesis imperfecta.