Early Onset and Rapid Progression of Dominant Nonsyndromic DFNA36 Hearing Loss

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.