Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder, clinically characterized by a variable degree of bone fragility with recurrent fractures, scoliosis, bone deformities, and short stature as well as non-skeletal abnormalities including blue sclerae, abnormal dentition, and joint hyperlaxity. Hearing loss is a common problem in patients with OI caused by type I (pro)collagen defects. On the basis of clinical and radiographic features, Sillence and colleagues  distinguished 4 OI subtypes, each representing a different phenotype with a mild (I), lethal (II), severe (III), and moderate (IV) severity. In most cases, the genotype is characterized by a heterozygous mutation in either the COL1A1 or COL1A2 gene. More uncommon, autosomal recessive forms caused by mutations in other genes have recently been discovered, but have not been associated with hearing loss. The genes COL1A1 and COL1A2 are both responsible for the formation of type I collagen, the major structural protein of bone, sclerae, ligaments, and tendons. Different mutation types may lead to various OI phenotypes. Nonsense, frameshift, and some splice site mutations result in a reduced synthesis of structurally normal type I collagen, also referred to as haploinsufficiency or a quantitative defect, and usually cause milder phenotypes (OI type I). In the more severe OI types (II-IV), mutations affect the structure of either the proα1(I) or proα2(I) chain and lead to the production of qualitatively abnormal collagen molecules. Glycine substitutions in the triple helical domain are the most common, but some splice site mutations leading to in-frame exon skips may also induce structurally impaired type I collagen. This group of mutations has a negative dominant effect. The overall clinical outcome depends on the type of impairment of type I collagen synthesis (quantitative or qualitative), the mutated gene, the substituting amino acid, and the location of the mutation in the triple helical domain [2, 3]. However, genotype-phenotype correlation studies have not been straightforward and inter- and intrafamilial variability in clinical characteristics partially remain unresolved .
The variability of the OI phenotype is also observed for the hearing loss and has long been a matter of study and debate. A variable prevalence of hearing loss in OI from 37 to 64% has been reported in family studies [5–11] and from 45 to 58% in nationwide population studies with systematic audiological evaluation [12–15]. In general, hearing loss in OI is believed to develop bilaterally as mild conductive hearing loss in the second to fourth decade of life, subsequently progressing to a mixed hearing loss with a severity ranging from mild to profound [8, 10, 13–17] Pure sensorineural hearing loss has been observed in a minority of OI patients.[8, 13, 15–17]. Like the majority of the characteristics inherent to the disease, OI-related hearing loss is apparently heterogeneous in occurrence, type, progression, severity, and underlying pathology. Although it has been suspected to be associated with a COL1A1 mutation  and to predominantly occur in the milder OI types [1, 19], no association has been demonstrated between the presence and type of hearing loss, and the OI subtype, the mutated gene or mutation type in a Finnish population of 47 unrelated OI patients with identified mutations in COL1A1 or COL1A2.
In the present study, audiological and genotypic characteristics as well as potential environmental risk factors for the development of hearing loss are investigated in a cohort of Belgian, Dutch, and Italian OI patients with familial or sporadic OI. In addition, inter- and intrafamilial variability in audiological features are studied.