Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve (postsynaptic AN), inner hair cells and/or the synapses with auditory nerve terminals (presynaptic AN). Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair-cell activities. Furthermore, AN can be identified either as an isolated disorder or as an associated disorder with multisystem involvement including peripheral and optic neuropathies (non-isolated AN). Mutations in several nuclear and mitochondrial genes have been identified as underlying these forms of AN. Recently, new genes have been identified as involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover, abnormal cochlear potentials have been recorded from patients with specific gene mutations by using acoustic stimuli or electrical stimulation through cochlear implant. In this review, different types of genetically based auditory neuropathies are discussed and the proposed molecular mechanisms underlying AN are reviewed.