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

Objective: To delineate the phenotype and genotype of an autosomal dominant low-frequency sensorineural nonsyndromic hearing impairment trait in relation to similar traits. Study Design: Family study, including retrospective case reviews. Setting: Tertiary referral center. Patients: Hearing impairment was documented in 11 family members in five generations, 8 of whom were alive and participated in this study. Intervention: Diagnostic. Main Outcome Measures: 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. Results: 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. Conclusion: A third family (designated Dutch 11) 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.