Aimoni C, Ciorba A, Cerritelli L, Ceruti S, Skarżyński P H, Hatzopoulos S
Clinic of Audiology & ENT, University of Ferrara, Italy.
Clinic of Audiology & ENT, University of Ferrara, Italy.
Int J Pediatr Otorhinolaryngol. 2017 Oct;101:254-258. doi: 10.1016/j.ijporl.2017.07.042. Epub 2017 Jul 29.
Enlarged Vestibular Aqueduct (EVA) is one of the most common congenital malformations associated with sensorineural or mixed hearing loss. The association between hearing loss and EVA is described in syndromic (i.e. Pendred Syndrome, BOR, Waardenburg) and non-syndromic disorders, as isolate or familiar mutations of the SLC26A4 gene. The audiological phenotype of the EVA syndrome is heterogeneous, the type and entity of hearing loss may vary and vertigo episodes might also be present.
The aim of this retrospective study was to describe the clinical and genetic features of a group of adolescent subjects presenting an EVA clinical profile, considering the presence of SLC26A4 gene mutations.
14 Caucasian patients were assessed (24 ears in total; 4 patients presented a monolateral EVA), 10 females and 4 males. Their age at the time of diagnosis was between 1 and 6 years (mean age 2.5 years). Subjects were assessed by an ENT microscopy evaluation with a complete audiometric assessment, CT & MRI scans and genetic tests for the evaluation of the pendrin gene mutations (SLC26A4).
Considering the presence of SLC26A4 mutations and thyroid function, we could identify three sub-groups of patients: group 1, non syndromic EVA (ns EVA, no SLC26A4 mutation and no thyroid dysfunction); group 2, EVA with DFNB4 (single SLC26A4 gene mutation and no thyroid dysfunction); group 3, EVA with Pendred Syndrome (two pathological mutation of SLC26A4 and thyromegaly with thyroid dysfunction). Patients of group 1 (ns-EVA) showed various degrees of hearing loss from mild (55%) to severe-profound (45%). In groups 2 (DFNB4) and 3 (PDS), the degree of hearing loss is severe to profound in 70-75% of the cases; middle and high frequencies are mainly involved.
The phenotypic expressions associated with the EVA clinical profile are heterogeneous. From the available data, it was not possible to identify a representative audiological profile, in any of the three sub-groups. The data suggest that: (i) a later onset of hearing loss is usually related to EVA, in absence of SLC26A4 gene mutations; and (ii) hearing loss is more severe in patients with SLC26A4 gene mutations (groups 2 and 3 of this study).
扩大的前庭导水管（EVA）是与感音神经性或混合性听力损失相关的最常见先天性畸形之一。听力损失与EVA之间的关联在综合征性疾病（如 Pendred 综合征、BOR、Waardenburg 综合征）和非综合征性疾病中均有描述，表现为 SLC26A4 基因的孤立或家族性突变。EVA 综合征的听力学表型具有异质性，听力损失的类型和程度可能不同，也可能出现眩晕发作。
本回顾性研究的目的是描述一组具有 EVA 临床特征的青少年受试者的临床和遗传特征，并考虑 SLC26A4 基因突变的存在情况。
评估了 14 名白种人患者（共 24 只耳；4 例为单侧 EVA），其中 10 名女性和 4 名男性。他们诊断时的年龄在 1 至 6 岁之间（平均年龄 2.5 岁）。通过耳鼻喉显微镜检查、全面的听力测定评估、CT 和 MRI 扫描以及用于评估 Pendrin 基因突变（SLC26A4）的基因检测对受试者进行评估。
考虑到 SLC26A4 突变的存在和甲状腺功能，我们可以将患者分为三个亚组：第 1 组，非综合征性 EVA（ns EVA，无 SLC26A4 突变且无甲状腺功能障碍）；第 2 组，伴有 DFNB4 的 EVA（单个 SLC26A4 基因突变且无甲状腺功能障碍）；第 3 组，伴有 Pendred 综合征的 EVA（SLC26A4 的两个病理性突变以及甲状腺肿大伴甲状腺功能障碍）。第 1 组（ns-EVA）患者表现出不同程度的听力损失，从轻度（55%）到重度至极重度（45%）。在第 2 组（DFNB4）和第 3 组（PDS）中，70-75%的病例听力损失程度为重度至极重度；主要累及中高频。
与 EVA 临床特征相关的表型表达具有异质性。根据现有数据，在这三个亚组中的任何一组中都无法确定具有代表性的听力学特征。数据表明：（i）在没有 SLC26A4 基因突变的情况下，听力损失较晚出现通常与 EVA 有关；（ii）SLC26A4 基因突变的患者（本研究的第 2 组和第 3 组）听力损失更严重。
