Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.

Auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs) are objective measures of auditory function, but are not hearing tests. Normal OAEs reflect normal cochlear outer hair cell function, and an ABR indicates a synchronous neural response. It is quite possible for a patient to have normal OAEs but absent or grossly abnormal ABR and a behavioral audiogram that is inconsistent with either test. These patients, who may constitute as much as 10% of the diagnosed deaf population, have auditory neuropathy/dys-synchrony (AN/AD). To diagnose AN/AD accurately, ABRs are obtained in response to condensation and rarefaction clicks to distinguish cochlear microphonics (CM) from neural responses. Appropriate management is confounded by variation among patients and changes in auditory function in some patients over time. Recommendations for management include visual language exposure through methods such as American Sign Language (ASL), Cued Speech, or baby signs, and closely following patients.

Genetic and auditory studies of 731 children with severe-to-profound hearing loss in US schools for the deaf and 46 additional children receiving clinical services for hearing loss ranging from moderate to profound demonstrated that mutations in the connexin 26 (GJB2) and connexin 30 (GJB6) genes explain at least 12% of those with nonsyndromic sensorineural deafness. Otoacoustic emissions (OAEs) testing to detect functional outer hair cells indicated that 76 of the children had emissions and therefore may have (as yet unconfirmed) auditory neuropathy/dys-synchrony (AN/AD). Five of these children with OAEs were GJB2 homozygotes or compound heterozygotes with the genotypes 35delG/35delG, W77X/W77X, 35delG/360delGAG, 35delG/V95M, and V84M/M34T. In particular, unilateral AN/AD was confirmed in a child with moderate hearing loss and the 35delG/V95M genotype. Detecting OAEs in individuals with GJB2 mutations suggests that lack of functional gap junctions as a result of GJB2 mutations does not necessarily destroy all outer hair cell function.

Neither auditory brainstem response (ABR) nor otoacoustic emissions (OAEs) are objective hearing tests, nor are their results always mutually consistent in any one patient. Therefore, it is quite possible for a patient to have normal emissions but absent or grossly abnormal ABR and behavioral audiograms that are inconsistent with either test. These patients, who may constitute as much as 10% of the diagnosed deaf population, are the subject of this article. To diagnose as many as possible properly from the onset, we urge triage (sorting or preselection by a system of priorities designed to maximize the effectiveness of treatment or outcome) using (1) tympanometry, (2) middle ear muscle reflexes, and (3) OAEs. Early diagnosis is essential because after either hearing aid use or the passage of time these patients often lose their OAEs and become almost indistinguishable from patients with ordinary deafness. Because auditory verbal therapy and hearing aids are rarely if ever successful with these patients until after cochlear implantation, it is essential to design intervention and interpret their audiograms physiologically rather than in conventional articulation index terms. This article offers management suggestions based on our experiences with close to 200 patients and their families. These suggestions include cued speech and baby signs for newborns. Cued speech gives them access to their parents' vocabulary and language, and the baby signs give them vocabulary to express needs and wants and remain linguistically attached. Then, if they are among the 93% of children who stay impaired, we have seen that cochlear implants are quite effective.