Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9

Objectives: Analysis of phenotype-genotype correlation. Study Design: Family study. Methods: Auditory and vestibule-ocular functions were examined in a Dutch family with autosomal dominantly inherited sensorineural hearing impairment caused by a 208C>T mutation in the COCH gene, located in chromosome 14q12-q13 (DFNA9). Linear regression analysis of individual longitudinal hearing threshold data (n = 11) on age was performed, Results: Fifteen of the 16 genetically affected persons could be evaluated. They all developed hearing and vestibular impairment symptoms-and in many cases also cardiovascular disease-in the fourth to fifth decade. At the low frequencies (0.25-2 kHz), hearing loss started at the age of about 40 years and showed an average annual progression of approximately 3 dB, finally resulting in profound hearing losses. In two exceptional cases, annual progression attained levels of up to 24 dB, At the high frequencies (4-8 kHz), the average threshold increased from about 50 dB at the age of 35 years to about 120 dB at the age of 15 years (which amounts to 1.8 dB annual threshold increase). All affected individuals tested showed normal ocular motor functions, The patients older than 46 years generally showed absence of the vestibule-ocular reflex, but their cervico-ocular reflex was enhanced compared with normal subjects, whereas those aged 40 to 46 years showed either severe vestibular hyporeflexia or unilateral caloric areflexia, Conclusion: These findings suggest a gradual development of cochleovestibular impairment caused by the new mutation found.