中文摘要：

目的研究和揭示大前庭水管综合征（Large vestibul araqueduct Syndrome，LVAS）的临床诊治策略。方法对2003年5月-2005年12月收集的107例大前庭水管综合征患者进行系统的临床听力学特征分析、影像学分析及SLC26A4致病基因检测分析，以期发现大前庭水管综合征患者的系列特征。临床听力学特征性观察包括纯音听力中低频的气骨导差；听性脑干诱发电位检查时观察特征性的声诱发短潜伏期负反应（acoustically evoked short latency negative response，ASNR）；影像学检查包括对所有患者均行颞骨CT扫描或耳蜗水成像磁共振检查了解前庭水管、内淋巴囊及耳蜗的发育情况；病因学分析包括应用聚合酶链反应（PCR）的方法扩增SLC26A4基因的21个外显子，直接测序，DNAStar及BioEdit序列比对软件分析SLC26A4基因的突变位点。结果70．8％～83．7％LVAS患者在低频500Hz、250Hz存在显著的气骨导差，范围在15～95dBHL。75．7％的LVAS患者在常规ABR测试时发现ASNR，潜伏期为3．26±0．57ms。97．9％的LVAS患者发生了SLC26A4基因的突变．其中双等位基因突变占88．4％，单等位基因和未发现突变的家系分别占9．5％和2．1％。共发现38种突变形式，包括23种国际上尚未报道的突变，15种已报突变（五种仅报道于中国家系）。其中IVS7—2A〉G突变是所有突变中最常见的突变，占所有突变者的78．9％，是中国人群中的特征性突变。影像学检查CT及磁共振是诊断LVAS的金标准。结论大前庭水管综合征具有特征性的纯音听力一低频气骨导差；具有特异性的ABR波形-ASNR；CT检查见前庭水管扩大。直径〉1．5mnl；具有特征性的MRI表现一扩大的内淋巴囊；具有特异和常见的SLC26A4基因突变谱。上述系列特征形成了对大前庭水管综合征的诊断依据。选择积极的治疗方案将有助于患者听力的保护与康复。

英文摘要：

Objective To study and disclose the reasonable strategy of diagnosis and treatment for large vestibular aqueduct syndrome （LVAS）. Methods One hundred and seven LVAS subjects recruited from May 2003 to Dec. 2005 were performed a clinical audiology analysis, imaging analysis as well as the SLC26A4 mutation screening for the purpose of finding a series of characteristics for diagnosis of LVAS. The audiological tests included play audiometry or pure tone audiometry, tympanometry, middle ear muscle reflex thresholds and stapedius muscle reflex （ acoustic and nonacoustic）, otoacoustic emissions （OAEs）, auditory brain stem responses （ABRs）. High-resolution computed tomography （CT） scan of the temporal bone and magnetic resonance imaging were used for understanding the structure of cochlea and endolymphatic sac. For investigating the pathogenesis of LVAS, genomic DNA was exatracted from peripheral blood. All 21 exons of the SLC26A4 gene were amplified by polymerase chain reaction （PCR）, then the PCR products were purified and directly sequenced. The sequences were analysed with DNAStar or BioEdit. Results 70.8-83.7% of LVAS patients were found to have a significant A-B gap at low frequencies （500 Hz and 250 Hz）, covering a span of 15-95 dB HL. In 75.7% of patients the short latency nagative response （ASNR） was evoked during the routine ABR testing. The latency of ASNRs was 3.26 ± 0.57 ms. In the present study, SLC26A4 gene mutations were detected in 97.9% of LVAS patients. Of these, 38 mutations were identified in the present study, including 23 novel mutations and 15 recurrent mutations including 5 mutations only appeared in Chinese population. Two mutant alleles were identified in 84 （88.4%） families. Families with one mutant allele and zero mutant allele accounted for 9.5% and 2.1%, respectively. One feature was that the IVS7-2A〉G mutation was detected in 75/95 families with LVAS and represents 57.63% of all mutant alleles. It is the commonest mutation in Chinese. CT scan combine