Letter to the editor regarding "hearing preservation and spatial hearing outcomes after cochlear implantation in children with tmprss3 mutations".

Dear Editor Peng et al. (1) describe sequential bilateral cochlear implantation in two siblings with down-sloping hearing loss due to compound heterozygous TMPRSS3 mutations. In both patients, implantation restored high-frequency hearing without damaging residual low-frequency acoustic hearing. We also have experience with TMPRSS3-related hearing loss and cochlear implant outcomes in individuals with this genotype and suggest the following. TMPRSS3-related hearing loss is highly progressive. In our recent study of pediatric hearing loss, we found TMPRSS3 to be the most progressive hearing loss of all genotypes tested, with a rate of decline of 37 dB/decade in pure-tone average (2). High frequencies were most severely affected, but progression occurred at all frequencies. Severity of TMPRSS3-related hearing loss was highly linked to mutation severity—patients with truncating (i.e., frameshift or nonsense) mutations presented with more rapid progression than patients with missense mutations, especially at lower frequencies such as 250 and 500 Hz (2). The two affected siblings outlined in Peng et al. are compound heterozygotes for one frameshift and one missense mutation, so their progression is predicted to be intermediate compared with other TMPRSS3 genotypes, ~64 dB/decade at 500 Hz and ~26 dB/decade at 250Hz (2). Peng et al. showed that low-frequency hearing was preserved immediately after sequential bilateral cochlear implantation in both siblings with TMPRSS3 mutations, with speech perception and sound localization metrics similar to or better than previously published data on bilateral cochlear implantees. According to the duplex theory of sound localization (3), sound location is encoded by the combination of interaural time differences (ITDs) and interaural level differences (ILDs). At least for pure tones, ITD dominates at low frequencies and ILD at high frequencies. Therefore, sound localization in patients with TMPRSS3-related hearing loss might benefit from bilateral implantation intended to restore lost high-frequency ILD perception without harming residual low-frequency ITD sensitivity. We believe, however, that this line of thinking is incomplete for two reasons. First, preservation of low-frequency acoustic hearing after implant is not guaranteed long term. In five patients with TMPRSS3-related hearing loss and unilateral cochlear implantation, all of whom retained low-frequency hearing immediately postoperatively, we found that residual hearing was preserved longer term in only three (Fig. 1), with two patients (I and V) experiencing sudden loss of acoustic hearing in the implanted ear months to years after implantation. Second, even in patients who retained low-frequency hearing longer term, this hearing continued to deteriorate rapidly. Similar progression also occurred in the unimplanted ears of all five individuals (Fig. 1).FIG. 1: Longitudinal audiometric thresholds at 500 Hz for individuals with TMPRSS3-related hearing loss before and after unilateral cochlear implantation. Each plot represents one individual (numeral above plot), with ear implanted and implant model indicated below plot. Vertical dotted lines indicate age at implantation and cochlear implant model. Individual V has a missense/missense compound heterozygous genotype; all others are frameshift/missense compound heterozygotes. All individuals had residual acoustic hearing at 500 Hz immediately after implant. Note sudden loss of residual hearing in the implanted ear in individuals I and V, and unclear results in individual II.This study and others indicate clearly favorable cochlear implant outcomes in patients with TMPRSS3-related hearing loss (1,2,4), and we share the authors’ enthusiasm for providing both ITD and ILD cues. However, we are not convinced of the benefits of early bilateral cochlear implantation for the specific purpose of improving binaural hearing in this population. Given the fragile nature of residual low-frequency hearing after implant, it may be more beneficial for these patients to receive a unilateral implant initially. The progressive nature of TMPRSS3 hearing loss mutations will likely eliminate low-frequency hearing and ITD discrimination in these individuals in a matter of years. Although their low-frequency hearing will be diminishing, it will initially support ITD-based sound localization and excellent bimodal hearing and music perception. Once progression in the unimplanted ear is sufficient, second-side cochlear implantation is then recommended. Ryan J. Carlson, Ph.D.Departments of Genome Sciences and Medicine University of Washington Seattle, Washington [email protected] Jay Rubinstein, M.D., Ph.D.Virginia Merrill Bloedel Hearing Research Center Department of Otolaryngology–Head and Neck Surgery University of Washington Seattle, Washington