Audiologic phenotype of osteogenesis imperfecta: use in clinical differentiation.

OBJECTIVES: To describe the audiologic phenotype in osteogenesis imperfecta (OI). STUDY DESIGN: Observational study. SETTING: Tertiary referral center. PATIENTS: One hundred eighty-two patients with genetically confirmed OI, aged 3 to 89 years. INTERVENTION: Diagnostic hearing evaluation through otoadmittance and acoustic stapedius reflex measurements, pure tone, and speech audiometry. MAIN OUTCOME MEASURE(S): Prevalence, type, severity, symmetry, and audiometric configuration of the hearing loss in OI. Progression of hearing thresholds was determined by constructing age-related typical audiograms. RESULTS: Approximately 52.2% of all OI patients demonstrated hearing loss unilaterally (7.7%) or bilaterally (44.5%). Pure conductive, mixed, and pure sensorineural hearing losses were observed in 8.5%, 37.8%, and 11.6% of OI ears, respectively. Multiple linear regression revealed that thresholds progressed by 0.5 dB/yr at 0.25 kHz to 0.8 dB/yr at 0.8 kHz in the ears with conductive or mixed hearing loss. Pure sensorineural hearing loss progressed by less than 0.1 dB/yr at 0.25 kHz to 1.2 dB/yr at 8.0 kHz. Audiometric configuration was predominantly flat (70.5%) in the ears with conductive/mixed loss and sloping (50.0%) in those with pure sensorineural loss. CONCLUSION: Patients with OI are at risk for hearing loss. The hearing loss in OI may initiate at a young age and is progressive. However, the rate of progression, as well as the hearing loss severity, onset, and configuration depend on the type of hearing loss, which may be conductive/mixed or pure sensorineural. For both types, age-related threshold audiograms are constructed and may help the clinician to estimate the course of the hearing loss in patients with OI. In addition, they may be valuable to distinguish between hearing loss associated with OI and other similar forms of hearing loss, such as in otosclerosis.

Osteogenesis Imperfecta: the audiological phenotype lacks correlation with the genotype.

BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable connective tissue disorder mainly caused by mutations in the genes COL1A1 and COL1A2 and is associated with hearing loss in approximately half of the cases. The hearing impairment usually starts between the second and fourth decade of life as a conductive hearing loss, frequently evolving to mixed hearing loss thereafter. A minority of patients develop pure sensorineural hearing loss. The interindividual variability in the audiological characteristics of the hearing loss is unexplained. METHODS: With the purpose of evaluating inter- and intrafamilial variability, hearing was thorougly examined in 184 OI patients (type I: 154; type III: 4; type IV: 26), aged 3-89 years, with a mutation in either COL1A1 or COL1A2 and originating from 89 different families. Due to the adult onset of hearing loss in OI, correlations between the presence and/or characteristics of the hearing loss and the underlying mutation were investigated in a subsample of 114 OI patients from 64 different families who were older than 40 years of age or had developed hearing loss before the age of 40. RESULTS: Hearing loss was diagnosed in 48.4% of the total sample of OI ears with increasing prevalence in the older age groups. The predominant type was a mixed hearing loss (27.5%). A minority presented a pure conductive (8.4%) or pure sensorineural (12.5%) loss. In the subsample of 114 OI subjects, no association was found between the nature of the mutation in COL1A1 or COL1A2 genes and the occurrence, type or severity of hearing loss. Relatives originating from the same family differed in audiological features, which may partially be attributed to their dissimilar age. CONCLUSIONS: Our study confirms that hearing loss in OI shows a strong intrafamilial variability. Additional modifications in other genes are assumed to be responsible for the expression of hearing loss in OI.