Department of Otorhinolaryngology, Chungbuk National University Hospital, Cheongju, Republic of Korea.
Department of Otorhinolaryngology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Otol Neurotol. 2023 Jun 1;44(5):e319-e327. doi: 10.1097/MAO.0000000000003880. Epub 2023 Apr 22.
To explore the phenotypes and genotypes of patients with branchio-oto-renal (BOR) and branchio-otic (BO) syndrome, and to analyze the middle ear surgery outcomes qualitatively and quantitatively, proposing a factor usefully prognostic of surgical outcomes.
Retrospective cohort study.
Tertiary referral center.
Eighteen patients with BOR/BO syndrome in 12 unrelated Korean families.
Middle ear surgery, including either stapes surgery or ossicular reconstruction.
Clinical phenotypes, genotypes, and middle ear surgery outcomes.
Eight probands (66.7%) were confirmed genetically; the condition segregated as a dominant or de novo trait. Six EYA1 heterozygous variants were identified by exome sequencing and multiplex ligation-dependent probe amplification. All variants were pathogenic or likely pathogenic based on the ACMG/AMP guidelines. Two novel EYA1 frameshift variants (p.His373Phefs4 and p.Gln543Asnfs90) truncating a highly conserved C-terminal Eya domain were identified, expanding the genotypic spectrum of EYA1 in BOR/BO syndrome. Remarkably, middle ear surgery was individualized to ensure optimal audiological outcomes and afforded significant audiological improvements, especially in BOR/BO patients without enlarged vestibular aqueducts (EVAs). A significant difference in air-bone gap closure after middle ear surgery was noted between the two groups even after adjusting for confounders: -20.5 dB in ears without EVAs (improvement) but 0.8 dB in ears with EVAs (no change or deterioration). Furthermore, the success rate was significantly associated with the absence of EVA.
The results of this study were against the notion that middle ear surgery is always contraindicated in patients with BOR/BO syndrome, and an EVA could be a negative prognostic indicator of middle ear surgery in BOR/BO patients. This may aid to determine the strategy of audiological rehabilitation in patients with BOR/BO syndrome.
探索并分析 branchio-oto-renal (BOR) 和 branchio-otic (BO) 综合征患者的表型和基因型，并对中耳手术结果进行定性和定量分析，提出一个对手术结果有预测价值的因素。
回顾性队列研究。
三级转诊中心。
12 个不相关的韩国家族中 18 名 BOR/BO 综合征患者。
中耳手术，包括镫骨手术或听骨链重建。
临床表型、基因型和中耳手术结果。
8 名先证者（66.7%）通过基因检测得到确认；该疾病呈显性或新生突变遗传特征。通过外显子组测序和多重连接依赖性探针扩增鉴定出 6 种 EYA1 杂合变异。根据 ACMG/AMP 指南，所有变异均为致病性或可能致病性。鉴定出两种新的 EYA1 移码变异（p.His373Phefs4 和 p.Gln543Asnfs90），导致高度保守的 Eya 结构域截断，扩大了 BOR/BO 综合征中 EYA1 的基因型谱。值得注意的是，为了确保最佳听力结果，对中耳手术进行了个体化设计，并且可以获得显著的听力改善，尤其是在没有扩大前庭水管（EVA）的 BOR/BO 患者中。即使在调整混杂因素后，中耳手术后气骨导差的闭合在两组之间仍有显著差异：无 EVA 的耳朵为 -20.5dB（改善），而有 EVA 的耳朵为 0.8dB（无变化或恶化）。此外，手术成功率与 EVA 的缺失显著相关。
该研究结果与中耳手术在 BOR/BO 综合征患者中总是禁忌的观点相悖，EVA 可能是 BOR/BO 患者中耳手术不良预后的一个指标。这可能有助于确定 BOR/BO 综合征患者的听力康复策略。
