儿童先天性长QT综合征20例致病基因和临床特征的单中心研究

Mutation spectrum and clinical features of congenital long QT syndrome in 20 children:a single center study

目的探讨儿童先天性长QT综合征(LQTS)的致病基因、临床特征及治疗随访情况。方法回顾性收集2011年4月15日至2021年4月15日山东大学附属省立医院小儿心脏科收治的20例诊断为先天性LQTS且行基因检测患儿的临床资料, 并采用独立样本t检验及Fisher′s确切概率法进行分析。结果 20例患儿均检出LQTS相关基因突变, 其中18例(90.0%)检出致病突变或疑似致病突变。检出LQTS突变基因5个, 分别为KCNQ1、KCNH2、SCN5A、CACNA1C、AKAP9。18例(90.0%)患儿有阳性症状, 其中13例(65.0%)有明确诱因。LQTS 1型(LQT1)患儿出现症状的诱因均与运动有关, 具有复合杂合突变的LQT1及Jervell-Lange-Nielsen综合征1型(JLNS1)晕厥诱因为运动或情绪激动;LQTS 2型(LQT2)的诱因与运动无关;LQTS 3型(LQT3)剧烈运动可出现症状;LQTS 8型(LQT8)为无诱因发作。20例患儿心电图校正QT(QTc)间期为(553.1±66.6) ms(460~707 ms), 其中17例QTc≥480 ms。各类型LQTS患儿心电图表现不一。QTc差异在不同性别、晕厥与无晕厥患儿中差异均无统计学意义(均P>0.05)。患儿随访时间(3.4±2.3)年(0~8.3年)。17例患儿接受治疗[β受体阻滞剂及植入型心脏复律除颤器(ICD)], 3例未接受治疗。至随访结束, 1例患儿死亡, 19例存活, 存活患儿中2例意识丧失。结论先天性LQTS基因诊断和临床诊断有较高的一致性。基因检测阳性率90.0%。临床表现、心电图特点因基因分型而异。β受体阻滞剂具有保护作用。口服药物治疗无效时, ICD治疗可防止心脏性猝死发生。

Objective To explore the pathogenic genes,clinical characteristics and treatment follow-up of children with congenital long QT syndrome(LQTS).Methods Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15,2011 to April 15,2021 in Department of Pediatric Cardiology,Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′s exact probability method.Results LQTS-related gene mutations were detected in all the 20 cases,and pathogenic or suspected pathogenic mutations were identified in 18 cases(90.0%).Five LQTS mutation genes were discovered,including KCNQ1,KCNH2,SCN5A,CACNA1C and AKAP9.Eighteen cases(90.0%)had positive symptoms,and 13 cases(65.0%)had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1)was related to exercise,the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1(JLNS1)with complex heterozygous mutations were exercise or emotional agitation;the causes of syncope in LQTS type 2(LQT2)were unrelated to exercise;severe exercise in LQTS type 3(LQT3)resulted in symptoms;and seizure in LQTS type 8(LQT8)was non-induced.The corrected QT(QTc)interval of 20 cases was(553.1±66.6)ms,with a range of 460-707 ms,among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG)manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders,or between children with syncope and those without syncope(all P>0.05).The follow-up time was(3.4±2.3)years,ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)]and 3 cases did not.By the end of the follow-up,1 child died,19 cases survived,and 2 cases of the surviving children lost consciousness.Conclusions There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.