title: Non-syndromic autosomal dominant progressive non-specific mid-frequency sensorineural hearing impairment with childhood to late adolescence onset (DFNA21).
abstract: An autosomal dominant trait of progressive, non-syndromic, non-specific mid-frequency sensorineural hearing impairment was identified in a Dutch family. Many affected family members (n = 21) 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 used 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 regression coefficient) was significant and fairly similar: the pooled value was about 1.0 dB/y. There was no significant (i.e. not =0 dB) offset threshold (i.e. Y intercept at age 0) found at any frequency. The regression lines could be pooled for the low frequencies (0.25-0.5 kHz) and the mid/high frequencies (1-8 kHz) and this produced apparent onset ages of about 3 and 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 range of at least 25-45 years). However, based on the longitudinal analysis of a patient from the age of 4 years onwards in some patients sensorineural hearing 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 chromosome 6p21-22.
authors.affiliation: Department of Otorhinolaryngology, University Hospital Nijmegen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Kunst
authors.forename: H
authors.initials: H
authors.lastname: Marres
authors.forename: P
authors.initials: P
authors.lastname: Huygen
authors.forename: G
authors.initials: G
authors.lastname: van Duijnhoven
authors.forename: A
authors.initials: A
authors.lastname: Krebsova
authors.forename: S
authors.initials: S
authors.lastname: van der Velde
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: F
authors.initials: F
authors.lastname: Cremers
authors.forename: C
authors.initials: C
authors.lastname: Cremers
mesh_terms: D000328:Adult; D017668:Age of Onset; D001299:Audiometry; D002648:Child; D002896:Chromosomes, Human, Pair 6; D003430:Cross-Sectional Studies; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012044:Regression Analysis