Autosomal dominant low-frequency hearing impairment (DFNA6/14): a clinical and genetic family study

To delineate the phenotype and genotype of an autosomal dominant low-frequency sensorineural nonsyndromic hearing impairment trait in relation to similar traits.

Family study, including retrospective case reviews.

Tertiary referral center.

Hearing impairment was documented in 11 family members in five generations, 8 of whom were alive and participated in this study.

Diagnostic.

Clinical study: medical and otologic history and examination, retrieval of previous audiograms, pure-tone audiometry, and statistical analysis of audiometric data. Genetic study: linkage analysis of blood samples in 18 clinically affected and nonaffected family members.

Hearing impairment had been present since early childhood, mainly affecting the low frequencies (mean threshold 45 dB HL at 0.25-1 kHz); speech recognition was hardly affected during the first three decades of life. Higher frequencies became involved with increasing age, thus causing a flat-type audiogram at middle age and down-sloping audiograms after age 60 years. Progression was mild but significant at all frequencies (0.5 dB/year at 0.25 kHz to 1.3 dB/year at 8 kHz) and persisted after correction was applied for normal presbyacusis. The trait was linked to chromosome 4p16.3, in a region comprising both the previously located, closely adjacent DFNA6 and the DFNA14 loci for low-frequency hearing impairment.

A third family (designated Dutch II) was identified with a low-frequency hearing impairment trait showing linkage to chromosome 4p16.3 (DFNA6/14). The progression of hearing impairment beyond presbyacusis in the current study is unprecedented for DFNA6/14 traits.