Chapter 12 - Collagenopathies: Osteogenesis imperfecta and related disorders

Abstract

Osteogenesis imperfecta (OI), also known as brittle bone disease, refers to a group of phenotypically and genetically heterogeneous connective tissue disorders most prominently characterised by multiple fractures leading to skeletal deformity and/or short stature, dentinogenesis imperfecta, hearing loss and blue sclerae. In over 85% of patients, OI is an autosomal dominant disorder caused by heterozygous mutations in COL1A1 [MIM120150] or COL1A2 [MIM120160] encoding, respectively, the α1(I) and α2(I) chains of type I collagen (Sillence et al., 1979) [1]. Discovery of recessive genes has resulted in a newer understanding about OI genetics, with about 20 different genetic causes now accounting for approximately 95% of cases (Lindahl et al., 2015) [2]. Sillence et al. in 1979 provided the clinical classification, which has been further expanded (Marini et al., 2017) [3]. The classification of OI has evolved over time corresponding to the newly identified genes. Traditionally, the diagnosis was mostly based on clinical evaluation and radiographic findings. However, with increased access to genetic testing and advances in genomic sequencing, genetics evaluation is now playing a key role in the diagnosis of OI.