Clinical and Genetic Characteristics of 18 Cases with Suspected Congenital Long QT Syndrome: A Retrospective Cross-Sectional Study

Abstract

Background: Long QT syndrome (LQTS) is characterized by prolonged QT interval in electrocardiogram (ECG), which is highly associated with sudden cardiac death (malignant arrhythmia). The purpose of this study was to explore the clinical and genetic characteristics of LQTS in children. Materials and Methods: Whole-exome sequencing and Sanger sequencing were performed in 18 probands with prolonged QT interval on the surface ECG. The pathogenicity of the detected variants was evaluated. Results: 44.4% (8/18) of patients were diagnosed with LQTS in the QT prolongation cohort, among which five variants in KCNQ1 and three in SCN5A were detected. Syncope was the primary manifestation. The mean QTc for variant-positive patients was 522 ± 36 ms and that for patients with negative results was 481 ± 15 ms. High probability (7/11, 63.6%) of LQTS presented among the patients with high Schwartz score (Schwartz score ≥3.5). Partial variant carrier parents had no symptoms but prolonged QTc on ECG. Besides, a case masquerading as epilepsy was reported. Conclusions: For a rapid and accurate diagnosis of LQTS, genetic testing should be combined with assessment of clinical information and ECG. Moreover, routine ECG examination is proposed in seizure patients to avoid misdiagnosis. Two novel variants in SCN5A were detected and the variant spectrum of which was expanded. Besides, we discuss incomplete penetrance and phenotypic heterogeneity of LQTS and suggest focusing on the variant carriers with no obvious symptoms.