Early onset and rapid progression of dominant nonsyndromic DFNA36 hearing loss

Otol Neurotol. 2004 Sep;25(5):714-9. doi: 10.1097/00129492-200409000-00011.


Objective: To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss.

Study design: Clinical evaluation of individuals with DFNA36 hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects.

Setting: Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations).

Patients: Thirteen affected members of a North American Caucasian family segregating DFNA36 hearing loss.

Main outcome measures: Pure-tone audiometric thresholds and their rates of progression.

Results: Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening.

Conclusions: DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Audiometry, Pure-Tone
  • Auditory Threshold / physiology*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Regression Analysis
  • Retrospective Studies