A Dominantly Inherited Progressive Deafness Affecting Distal Auditory Nerve and Hair Cells

We have studied 72 members belonging to a large kindred with a hearing disorder inherited in an autosomal dominant pattern. We used audiological, physiological, and psychoacoustic measures to char-acterize the hearing disorders. The initial phenotypic features of the hearing loss are of an auditory neu-ropathy (AN) with abnormal auditory nerve and brainstem responses (ABRs) and normal outer hair cell functions [otoacoustic emissions (OAEs) and cochlear microphonics (CMs)]. Psychoacoustic stud-ies revealed profound abnormalities of auditory temporal processes (gap detection, amplitude mod-ulation detection, speech discrimination) and fre-quency processes (difference limens) beyond that seen in hearing impairment accompanying cochlear sensory disorders. The hearing loss progresses over 10–20 years to also involve outer hair cells, producing a profound sensorineural hearing loss with absent ABRs and OAEs. Affected family members do not have evidence of other cranial or peripheral neur-opathies. There was a marked improvement of audi-tory functions in three affected family members studied after cochlear implantation with return of electrically evoked auditory brainstem responses (EABRs), auditory temporal processes, and speech recognition. These findings are compatible with a distal auditory nerve disorder affecting one or all of the components in the auditory periphery including terminal auditory nerve dendrites, inner hair cells, and the synapses between inner hair cells and audi-tory nerve. There is relative sparing of auditory gan-glion cells and their axons