A number of conditions are associated with fragile bones and the classification of these in the early literature is confusing. More confusion arises from classification schemes based solely on clinical degrees of severity.
The designation ‘osteogenesis imperfecta’ is most accurately applied to disorders caused by construction defects in type I collagen fibers which are responsible in 90% of affected individuals. The defect may occur in either the pro-alpha 1 or pro-alpha 2 chains which together form type I collagen. The responsible genes are COL1A1 (17q21.31) and COL1A2 (7q22.1). Clinical types I (166200), IIA (166210), III (259420), and IV (166220) map to these two loci. The inheritance pattern is autosomal dominant.
Mutations in the CRTAP gene (610854; 3p22) cause an autosomal recessive OI-like phenotype classified as type VII while type VIII is an autosomal recessive OI-like disorder secondary to mutations in LEPRE1 (610915; 1p34). However, these disorders, while clinically sharing some features of true OI, are better designated as separate conditions based on their unique molecular etiologies.