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.