INHERITED NONSYNDROMIC HEARING-LOSS - AN AUDIOVESTIBULAR STUDY IN A LARGE FAMILY WITH AUTOSOMAL-DOMINANT PROGRESSIVE HEALING LOSS RELATED TO DFNA2

Objective: To study nonsyndromic progressive sensorineural hearing los s (SNHL) with significant linkage to the DFNA2 locus on chromosome 1p in a Dutch kindred. Design: A 6-generation family with 194 family memb ers was studied. Of the presumably affected persons, 43 were examined in detail to obtain audiograms and 37 underwent vestibule-ocular exami nation. Results: Regression analysis showed significant and equal line ar progression in SNHL with age (by about 1 dB per year) at all freque ncies. Offset values were close to zero at the low frequencies (0.25, 0.5, and 1 kHz) but increased systematically with the frequency. It is likely that they represent congenital high-frequency SNHL: about 15 d B at 2 kHz, 30 dB at 4 kHz, and 50 dB at 8 kHz. Bilateral caloric weak ness was not observed. A significant finding was that 25% to 35% (depe nding on the exclusion criteria) of the patients showed an increased v estibule-ocular reflex (hyperreactivity) as measured by rotatory respo nses. Forty-one patients showed significant linkage to the 1p locus. C onclusions: Including the present family, 4 families have been reporte d to show linkage to chromosome 1p. Statistical analysis of the audiol ogical data shows a progression of 1 dB per octave per year in this ty pe of progressive SNHL.