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

Clin Otolaryngol Allied Sci. 2000 Feb;25(1):45-54. doi: 10.1046/j.1365-2273.2000.00327.x.


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.

MeSH terms

  • Adult
  • Age of Onset
  • Audiometry
  • Child
  • Chromosomes, Human, Pair 6*
  • Cross-Sectional Studies
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Regression Analysis