Non-syndromic autosomal dominant progressive non-specific mid-frequency sensorineural hearing impairment with childhood to late adolescence onset (DFNA21)

An autosomal dominant trait of progressive, non-syndromic, non-specific mid -frequency sensorineural hearing impairment was identified in a Dutch famil y. Many affected family members (n = 10) were identified, among whom seven out of nine relatives aged <30 years do not show pure mid-frequency hearing impairment, which suggests variable expression. Regression analysis was us ed to evaluate the age-related hearing threshold data in a cross-sectional analysis in 24 affected patients and in a longitudinal analysis in five of these. At all frequencies, progression in hearing impairment (i.e. the regr ession coefficient) was significant and fairly similar: the pooled value wa s about 0.9 dB/y. There was no significant (i.e. not equal 0 dB) offset thr eshold (i.e. Y intercept at age 0) found at any frequency. The regression l ines could be pooled for the low frequencies (0.25-0.5 kHz) and the mid/hig h frequencies (1-8 kHz) and this produced apparent onset ages of about 3 an d 4 years and annual threshold increases of 0.75 and 1.1 dB/y, respectively . In most patients there is a relatively late onset age (maximum in the ran ge of at least 25-45 years). However, based on the longitudinal analysis of a patient from the age of 3 years onwards in some patients sensorineural h earing impairment might be congenital/prelingual. Oculo-vestibular function was found to be normal. Results from linkage studies tentatively position the underlying gene defect telomeric to the repositioned DFNA13 locus at ch romosome 6p21-22.