儿童先天性长QT综合征58例临床特征及治疗分析

Clinical characteristics and treatment of congenital long QT syndrome in 58 children

目的探讨儿童先天性长QT综合征(LQTS)的临床特征、致病基因及疗效。方法回顾性分析2013年8月至2017年11月清华大学第一附属医院心脏中心小儿科收治的被诊断为LQTS的58例患儿[男37例,女21例,诊断年龄(8.0±4.1)岁,范围0.1~16.0岁]的临床资料及治疗随访情况。评估每例患儿的病史、体表心电图、心脏超声、动态心电图、超声心动图、致病基因的筛查结果。结果48例(83%)LQTS患儿曾被漏诊或误诊,延迟诊断时间为0.7(0.1,2.0)年,诊断QTc延长待查10例(17%),复杂心律失常27例(47%),心肌炎、晕厥待查各3例(5%),癫痫2例(3%),心肌梗死、心肌病、血管迷走性晕厥各1例(2%)。9例有阳性家族史,3例合并先天性神经性耳聋。21例(36%)患儿有晕厥发作,14例为运动和(或)情绪激动诱发。心律失常类型依次为室性心律失常26例(45%)、病态窦房结综合征18例(31%)、房室传导阻滞(AVB)12例(21%)、房性心律失常6例(10%)。41例(71%)患儿发现LQTS相关的致病或可能致病的突变基因。33例(57%)患儿接受治疗,22例接受单一普萘洛尔治疗;9例植入永久起搏器治疗,其中5例同时服用普萘洛尔;2例植入心脏复律除颤器并服用普萘洛尔。显效18例(55%),有效13例(39%)。随访时间为1.7(0.5,2.4)年,1例死亡(2%)。结论儿童LQTS恶性度高,临床表型多样,呈现为复杂心律失常。致病或可能致病的突变基因检出率较高。β受体阻滞剂可有效降低恶性心脏事件的发生,部分患儿需接受心脏起搏器或植入型心脏复律除颤器治疗。

Objective To assess the clinical characteristics, pathogenic genes and therapeutic effects of congenital long QT syndrome (LQTS) in children. Methods A retrospective analysis included 58 LQTS children (37 boys, 21 girls;age of diagnosis (8.0±4.1) years, range 0.1 to 16.0 years) at Division of Pediatric Cardiology, First Hospital of Tsinghua University from August 2013 to November 2017. Each patient was evaluated with a detailed medical history, 12-lead resting electrocardiogram, Doppler echocardiography, and molecular genetic analysis. Results Forty-eight of the children (83%) had a delay to diagnosis (0.7 (0.1, 2.0)years) and initially received a misdiagnosis. QT prolongation of unknown origin was found in 10 cases (17%), complex arrhythmic conditions in 27 cases (47%), myocarditis in 3 cases (5%), syncope of unknown origin in 3 cases (5%), epilepsy in 2 cases (3%), myocardial infarction in 1 case (2%), cardiomyopathy in 1 case (2%), and vasovagal syncope in 1 case (2%). Nine children presented with the positive family history of LQTS and three children had congenital nervous deafness. Twenty-one (36%) children presented with recurrent syncope, and 14 cases of whom had symptoms during physical activity and/or emotional stress. The common arrhythmias were ventricular arrhythmia (26 cases), sinus node dysfunction (18 cases), atrioventricular block (AVB)(12 cases), and atrial arrhythmia (6 cases). LQTS-associated pathologic or possibly pathologic mutations were found in 41 children (71%). Thirty-three children (57%) were treated with propranolol (22 cases), permanent pacemaker (PM) combined with propranolol (5 cases), PM (4 cases), and implantable cardioverter defibrillator (ICD) combined with propranolol (2 cases). Eighteen children (55%) were asymptomatic, thirteen children (39%) reported infrequent syncope, and one case (2%) died. Conclusions LQTS in children is potentially malignant and present as phenotypic diversity and complex arrhythmias. LQTS-related pathogenic or possibly pathogenic mutations are identified in most of the children. Beta-blockers therapy is effective in reducing the risk of malignant cardiac events. Some children with LQTS should receive PM or ICD therapy.