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

Objectives: Analysis of phenotype-genotype correlation. Study Design: Famil y study. Methods: Auditory and vestibule-ocular functions were examined in a Dutch family with autosomal dominantly inherited sensorineural hearing im pairment caused by a 208C>T mutation in the COCH gene, located in chromosom e 14q12-q13 (DFNA9). Linear regression analysis of individual longitudinal hearing threshold data (n = 11) on age was performed, Results: Fifteen of t he 16 genetically affected persons could be evaluated. They all developed h earing and vestibular impairment symptoms-and in many cases also cardiovasc ular 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 avera ge annual progression of approximately 3 dB, finally resulting in profound hearing losses. In two exceptional cases, annual progression attained level s 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 ag e of 15 years (which amounts to 1.8 dB annual threshold increase). All affe cted 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 subject s, whereas those aged 40 to 46 years showed either severe vestibular hypore flexia or unilateral caloric areflexia, Conclusion: These findings suggest a gradual development of cochleovestibular impairment caused by the new mut ation found.