目的 对先天性长QT 综合征（LQTS）患儿临床表型及基因变异谱进行总结分析，探讨LQTS基因型与临床表型的潜在相关性。方法 选取2018年11月至2023年11月心内科收治的14个无亲缘关系的LQTS家系作为研究对象，收集患儿的临床资料，对患儿进行家系全外显子组测序，应用Sanger测序验证候选变异，并对患儿进行治疗和随访。结果 14例患儿中男6例、女8例，中位发病年龄为82.5（37.5~129.8）个月。14例以心跳骤停、晕厥或阿斯综合征发病。共检出5个基因（KCNQ1、KCNH2、SCN5A、CACNA1C和CALM1基因）的相关变异，依据美国医学遗传学与基因组学学会（ACMG）相关变异评级指南，变异位点均为致病性变异或可能致病性变异。其中，SCN5A基因（NM_198056.2）c.796C>G（p.Leu266Val）变异既往未见文献报道，依据ACMG指南评级为可能致病变异（PS2+PM2_Supporting+PP3）。14例患儿均用β受体阻滞剂治疗，其中2例联用美西律治疗；随访至2024年3月31日，3例死亡；1例因自行停药而导致阿斯综合征发作1次，余均未再出现晕厥。结论 本研究发现了一个SCN5A基因的新变异c.796C>G（p.Leu266Val），拓展了先天性LQTS相关SCN5A基因变异谱。先天性LQTS发病形式多样，对于疑似LQTS的患儿应进行心电图检查，并结合基因检测可对疾病明确诊断。

Objective The clinical phenotype and gene variation spectrum of children with congenital long QT syndrome (LQTS) were summarized and analyzed to explore the potential correlation between LQTS genotype and clinical phenotype. Methods Fourteen unrelated LQTS families admitted to the Department of Cardiology from November 2018 to November 2023 were selected as the study objects. The clinical data of the children were collected, whole exome sequencing of family was performed, candidate variants were verified by Sanger sequencing, and the children were treated and followed up. Results The median onset age of the 14 patients (6 boys and 8 girls) was 82.5 (37.5-129.8) months. Fourteen patients started with sudden cardiac arrest, syncope or Adams-Stokes syndrome. A total of 5 genes (KCNQ1, KCNH2, SCN5A, CACNA1C, and CALM1) were detected with variations, and according to the grading standard of the American College of Medical Genetics and Genomics (ACMG), all variations were pathogenic or likely pathogenic. Among them, SCN5A (NM_198056.2) c.796C>G (p.Leu266Val) has not been reported in the literature in the past, and according to the ACMG guidelines, it is determined to be a likely pathogenic variant (PS2+PM2_Supporting+PP3). All 14 children were treated with β-blockers, 2 of whom were also treated with mexiletine. During follow-up until March 31, 2024, there were 3 deaths. One child had an episode of Adams-Stokes syndrome due to self-discontinuation of medication, and the remainder had no further syncope. Conclusions In this study, a novel variant c.796C>G (p.leu266val) of SCN5A gene was found, expanding the spectrum of SCN5A gene variants associated with congenital LQTS. There are various forms of congenital LQTS, and an electrocardiogram should be performed for children with suspected LQTS, which in combination with genetic testing can lead to a definitive diagnosis of the disease.