Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Factors influencing auditory brainstem response changes in infants.

BACKGROUND: To elucidate the factors influencing auditory brainstem response (ABR) threshold improvement in infants. METHODS: This retrospective study included 626 infants who underwent ABR at the our Health and Medical Center between 2016 and 2020. Preliminary assessment indicated that 352 infants had an ABR threshold ≥40 dBnHL in both ears. A second ABR examination was conducted 5 months after delivery. The participants were divided into the improved (improvement ≥20 dBnHL) and unchanged (improvement <20 dBnHL) groups. The associations between risk factors were evaluated. Furthermore, we measured and compared the latencies of waves I, III, and V between participants with normal hearing and those in the improved and unchanged groups. RESULTS: The improved and unchanged groups consisted of 185 and 167 participants, respectively. ABR deterioration occurred in one infant with unilateral congenital cytomegalovirus-associated hearing loss. Binary logistic regression analysis revealed that the presence of otitis media with effusion and Down syndrome were factors contributing to ABR threshold improvement. In the ABR waveform analysis, patients in the improved group who had otitis media with effusion exhibited prolonged latencies of waves I, III, and V. Conversely, patients in the unchanged group who had Down syndrome showed shortened I-V interval. CONCLUSIONS: Half of the infants tested the second time showed improvement in ABR threshold. Children with congenital syndromes (such as Down syndrome) or otitis media with effusion should undergo a second ABR examination or other auditory assessments to ensure an accurate diagnosis of hearing loss.