大前庭水管综合征患儿的听力学及致病基因特征

Audiology and Pathogenic Genes Characteristics in Children with Large Vestibular Aqueduct Syndrome

目的总结分析大前庭水管综合征(large vestibular aqueduct syndrome,LVAS)患儿的听力学和致病基因特点,为早期诊断、干预及遗传咨询提供依据。方法回顾性分析2016年1月—2021年6月郑州大学第一附属医院0~10岁经颞骨高分辨CT或薄层MRI确诊的39例(78耳)LVAS患儿的听力学及耳聋基因检测资料。结果有26例51耳(65.38%)听性脑干反应(auditory brainstem response,ABR)测试在3 ms附近能记录到特异性的声诱发短潜伏期负反应(acoustically evoked short latency negative response,ASNR);39例78耳畸变产物耳声发射(distortion product otoacoustic emission,DPOAE)均未引出;鼓室导抗图均为A型或正向单峰,6耳可以引出声反射;28例(56耳)能够配合主观测听的患儿中42耳(75%,42/56)表现为低中频(<2 kHz以下)存在明显气-骨导差而高频下降型的混合性听力损失;听性稳态反应(auditory steady-state response,ASSR)在12例(24耳)ABR最大强度未引出患儿中的引出率为21耳(87.5%);耳聋基因共检出SLC26A4基因纯合突变21例,复合杂合突变18例。结论中耳功能正常时,主观测听显示低中频存在气-骨导差及ABR可以引出ASNR,这些听力学特征性结果有助于患儿LVAS的早期诊断;ABR最大输出强度各波消失时,ASSR测试可评估患儿的残余听力;对SLC26A4基因全编码区序列进行检测分析是明确LVAS患儿遗传学病因的有效手段。

Objective To report audiology and pathogenic genes characteristics in infants and children with large vestibular aqueduct syndrome(LVAS),to provide basis for early diagnosis,intervention and genetic counseling.Method Audiology and deafness gene test data were retrospectively analyzed in 39 children(0-10 years old,78 ears)with large vestibular aqueduct syndrome diagnosed by HRCT or MRI.Results ABR tests showed specific acoustically evoked short latency negative responses(ASNRs)at 3ms in 26 cases(51 ears,64.56%).DPOAEs were negative in all 78 ears.Tympanometry was type A with a single positive pressure peak in all ears,with acoustic reflex obtainable in 6 ears.Twenty eight children(56 ears)were able to cooperate in audiometry,in whom 42 ears(75%)demonstrated airbone gap over low to mid frequencies(<2 kHz)and mixed high frequency loss.In the 12 cases(24 ears)in which ABRs were absent at the maximum stimulus output,auditory steady-state responses(ASSRs)were obtainable in 21 ears(87.5%).A total of 21 homozygous mutations and 18 complex heterozygous mutations of the SLC26A4 gene were detected.Conclusion Audiologic features in children with LVAS may include normal middle ear function with pure tone audiometry showing air-bone gap over low to mid frequencies and ABR test showing ASNRs,which can be used for early diagnosis of LVAS.In the case of absent ABRs,ASSRs can be used to assess residual hearing in these children.Analysis of the SLC26A4 gene full coding region sequence is an effective means to identify the genetic etiology in children with LVAS.