Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.

Mutations in the potassium channel gene KCNQ4 underlie DFNA2, a subtype of autosomal dominant progressive, high-frequency hearing loss. Based on a phenotype-guided mutational screening we have identified a novel mutation c.886G>A, leading to the p.G296S substitution in the pore region of KCNQ4 channel. The possible impact of this mutation on total KCNQ4 protein expression, relative surface expression and channel function was investigated. When the G296S mutant was expressed in Xenopus oocytes, electrophysiological recordings did not show voltage-activated K(+) currents. The p.G296S mutation impaired KCNQ4 channel activity in two manners. It greatly reduced surface expression and, secondarily, abolished channel function. The deficient expression at the cell surface membrane was further confirmed in non-permeabilized NIH-3T3 cells transfected with the mutant KCNQ4 tagged with the hemagglutinin epitope in the extracellular S1-S2 linker. Co-expression of mutant and wild type KCNQ4 in oocytes was performed to mimic the heterozygous condition of the p.G296S mutation in the patients. The results showed that the G296S mutant exerts a strong dominant-negative effect on potassium currents by reducing the wild type KCNQ4 channel expression at the cell surface. This is the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2.

Subtotal petrosectomy in cochlear implantation permits obtaining a cavity isolated from the external environment, and when needed, it improves the access and visibility during the surgical procedure. Subtotal petrosectomy is a safe technique, with a low rate of complications.

The aim of this study was to evaluate the cochlear implant (CI) performances in neurofibromatosis type 2 (NF2) patients with bilateral vestibular schwannoma (VS) and in patients with sporadic VS in the only or better hearing ear. All patients with bilateral VS or sporadic VS in the only or better hearing ear who underwent cochlear implantation, either simultaneous to VS surgery or staged after treatment for VS, in the tumor side were chosen for the study. Postimplantation audiometric scores (sound detection, closed-set and open-set discrimination scores) and device use patterns were the main outcome measures. 15 patients were implanted. Eight patients (53 %) were NF2 and seven patients had VS in the only or better hearing ear. One patient was explanted for cerebrospinal fluid leak. In the CI-only condition, the other 14 patients obtained sound detection, 64 % of them achieving open-set discrimination (mean 70 ± 38 %) and 85 % achieving closed-set discrimination (mean 41 ± 33 %). At the last follow-up 10 patients (67 %) were using the CI. Cochlear implantation provides hearing in particular cases of patients with bilateral VS or VS in the only or better hearing ear. As long as anatomic preservation of the cochlear nerve is achieved, cochlear implantation may offer improvement in communication skills for most patients.

In most cases, cochlear implantation is a straightforward procedure. Nevertheless, there are clinical situations in which the presence of the middle ear may compromise access and/or the outcome in terms of complications. This article includes a series of patients for whom we eliminated the middle ear to facilitate placement of the electrode array of the implant and/or reduce potential complications. A total of 92 cases in 83 patients, managed by the senior author, are included in this series. Different indications are outlined that justify associating a subtotal petrosectomy technique with cochlear implantation. The steps of the technique are described. We include complications from this series that compare favorably with standard techniques.