耳聋-甲状腺肿综合征的临床诊断及分子病因分析  

Clinical diagnosis and genetic testing for Pendred syndrome

作　　者：袁永一[1] 黄莎莎[1] 左路杰[2] 张国正[1] 戴朴[1,3] 

机构地区：[1]解放军总医院耳鼻咽喉-头颈外科,北京100853 [2]河北省儿童医院耳鼻喉科,石家庄050030 [3]解放军总医院海南分院耳鼻咽喉头颈外科,海南572000

出　　处：《中华耳科学杂志》2014年第1期15-18,共4页Chinese Journal of Otology

基　　金：国家十二五支撑项目(2012BAI09B00;2012BAI12B01);国家自然科学基金重点项目(81230020);国家自然科学基金面上项目(81371096;81371098);卫生部行业专项基金(201202005);北京市自然科学基金面上项目(7132177;7122172);北京市科技新星计划(2009B34;2010B081);国家高技术研究发展计划("863";2012AA020101)

摘　　要：目的分析耳聋-甲状腺肿综合征（Pendred综合征）的临床特点和分子诊断特征，以加强耳鼻喉科医生对本病的认识，减少漏诊、误诊。方法调查2003年1月-2013年12月在解放军总医院聋病分子诊断中心就诊的前庭水管扩大耳聋患者1745人，对其中体格检查发现甲状腺肿大的患者行甲状腺超声、甲功五项、过氯酸盐释放试验及PDS基因测序。结果共诊断4例Pendred综合征，4例患者甲状腺肿表型均出现于11岁后，甲状腺功能检查无明显异常，B超检查提示甲状腺肿伴甲状腺结节，过滤酸盐释放试验证实3人有甲状腺碘有机化障碍，1人结果在正常范围。接受基因筛查的3人均被证实携带PDS基因双等位基因突变，PDS基因缺陷是其分子病因。结论Pendred综合征在中国的发病率可能并不低，部分Pendred综合征病人因就诊时甲状腺表型尚未显现或医生经验不足而出现漏诊。对于临床就诊的低龄EVA患者应常规检查甲状腺并告知其随访。基因诊断是Pendred综合征诊断的重要依据，对患者父母再生育前产前诊断及患者本人婚配前遗传咨询具有重要指导意义。Objective To analyze the clincial traits and genetic testing for Pendred syndrome and tohelp ENT doctors understand the disease and avoid misdiagnosis and missed diagnosis. Methods 1,745 patients with enlarged vestibular aque- duct verified by high resolution temporal bone CT scan were included. After careful physical examination, ultrasound scan of thyroid, thyroid hormone assays and the perchlorate discharge test were performed on subjects with bilateral EVA and goiter. Results Pendred syndrome was diagnosed in four patients. They all showed goiter, sensorineural hearing loss and EVA. The goiter all appeared after 11 years old in these Pendred syndrome patients. Three of them were verified thyroid iodine organifi- cation defect by perchlorate discharge test. The thyroid hormone levels were all within the normal range. PDS gene sequenc- ing was carried out in 3 of the Pendred syndrome patients and these patients were all found carrying homozygous or compound heterozygous PDS mutations. Conclusions Since the phenotype of goiter didn＇ t emerge at the time the Pendred syndrome patients came to the clinic, or the doctors hadn＇ t enough experience on Pendred syndrome, there are still missed diagnosis on the disease in China. And the ratio of Pendred syndrome may be not so low as that shown by our study. We suggest that chil- dren EVA patients should be given instruction for follow-up of the thyroid. Genetic testing is one of the major factors for diag- nosing Pendred syndrome. It＇ s important for the normal hearing parents who had given birth to a Pendred syndrome baby and are in need of repregnancy. It＇ s also significant for Pendred syndrome patients in need of genetic counseling before marriage and pregnancy.

关 键 词：耳聋一甲状腺肿综合征(Pendred综合征) 分子诊断 临床特点 

分 类 号：R764.04[医药卫生—耳鼻咽喉科]