关键词: 先天性长QT综合征, SCN5A基因, 变异

Abstract:

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.

Key words: congenital long QT syndrome, SCN5A gene, variation