González-Aguado Rocío, Fernández-Enseñat Julia, Onecha Esther, Morales-Angulo Carmelo
Department of Otolaryngology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain.
Department of Genetics, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain.
Eur Arch Otorhinolaryngol. 2025 Apr 3. doi: 10.1007/s00405-025-09288-x.
Heterozygous variants of the KCNQ4 gene are associated with isolated sensorineural hearing loss (DFNA2A). This study aimed to determine the frequency and clinical characteristics of pathogenic, likely pathogenic, and uncertain variants in the KCNQ4 gene among patients with sensorineural hearing loss of unknown origin in North Spain.
We conducted a prospective observational study of patients with sensorineural hearing loss of unknown etiology at a tertiary hospital over six years. Next-generation sequencing carried out with a panel of genes was used to identify genetic variants related to both syndromic and non-syndromic hearing loss.
Among 370 patients, seven (1.89%) harbored pathogenic or likely pathogenic variants in the KCNQ4 gene: c.777_778delinsCC, c.626 T > G, and c.778G > C. None of these variants had been previously described. One patient also had a variant of uncertain significance (c.419 T > C). All patients exhibited progressive bilateral sensorineural hearing loss, predominantly at high frequencies, with variable onset and severity. None reported dizziness or vertigo. Five patients used hearing aids, and one received a cochlear implant with good results.
KCNQ4 gene variants are rare in Cantabria, present in less than 2% of patients with sensorineural hearing loss of unknown origin. Although most variants identified in our study had not been previously described, the observed phenotype aligned with the typical presentation: bilateral, progressive sensorineural hearing loss with variable onset and severity. Some patients may benefit from cochlear implants.
KCNQ4基因的杂合变异与孤立性感音神经性听力损失（DFNA2A）相关。本研究旨在确定西班牙北部不明原因感音神经性听力损失患者中KCNQ4基因的致病、可能致病及意义未明变异的频率和临床特征。
我们在一家三级医院对病因不明的感音神经性听力损失患者进行了为期六年的前瞻性观察研究。使用一组基因进行的二代测序用于识别与综合征性和非综合征性听力损失相关的基因变异。
在370例患者中，7例（1.89%）在KCNQ4基因中携带致病或可能致病变异：c.777_778delinsCC、c.626 T>G和c.778G>C。这些变异此前均未被描述过。1例患者还存在意义未明的变异（c.419 T>C）。所有患者均表现为双侧进行性感音神经性听力损失，主要为高频听力损失，起病和严重程度各异。均未报告头晕或眩晕。5例患者使用了助听器，1例接受了人工耳蜗植入，效果良好。
KCNQ4基因变异在坎塔布里亚地区较为罕见，在不明原因感音神经性听力损失患者中的比例不到2%。尽管我们研究中鉴定出的大多数变异此前未被描述过，但观察到的表型与典型表现一致：双侧、进行性感音神经性听力损失，起病和严重程度各异。一些患者可能从人工耳蜗植入中获益。
