The phenotype of DFNA13/COL11A2: Nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment

Objective: To study nonsyndromic progressive sensorineural hearing impairme nt in patients with a COL11A2 mutation (DFNA13) in a Dutch kindred. Study Design: Survey. Setting: Department of otorhinolaryngology of a university hospital. Patients: Twenty-one living members of a Dutch family (150 relatives in 5 g enerations; 49 were studied) with autosomal dominant nonsyndromic sensorine ural hearing impairment showed linkage to the DFNA13 locus. Mutation analys is revealed a missense mutation in the COL11A2 gene. Methods: History was taken, hearing threshold levels were measured in all a ffected persons, and penetrance was evaluated. Longitudinal analysis (using linear regression analysis of threshold-on-age data) was possible in only 1 case. Cross-sectional analysis comprised the comparison of threshold leve ls between different generations of the family. Also, hearing thresholds we re corrected for median presbyacusis to find out whether the hearing impair ment characteristic of this trait is stationary or progressive. Vestibular functions were evaluated with electronystagmography, by use of rotatory and caloric tests. Results: Most of the affected persons dated their first hearing impairment symptoms to the second to third decade of life. A possibly reduced penetran ce was found. Anamnestically, 4 affected persons had hearing impairment sym ptoms from early childhood onward. Longitudinal analysis in the proband (IV 26) revealed the exceptional combination of congenital offset and substanti al early progression. Most of the threshold levels differed significantly b etween the frequencies within each age group and, at the high frequencies ( 2-8 kHz), between the two age groups covered by generations IV and III (age s 30-38 years and 58-74 years, respectively); the latter could be attribute d to presbyacusis. Various caloric abnormalities, including areflexia, were found in about half (8/17) of the tested subjects with sensorineural heari ng impairment. Conclusions: Correction for age, hearing impairment-presumably present and stationary from an early age onward-showed the worst or second-worst thresh old usually at 1, 2, and 6 kHz (35-40 dB) or 8 kHz (50 dB), whereas the bes t or second-best threshold was found at 0.25 to 0.5 and 4 kHz (25 dB). Pres byacusis, presumably from the fourth decade of life onward, caused a change of the typically shaped audiogram described as midfrequency hearing impair ment with additional high-frequency impairment.