Study of the diagnostic yield of gene panels in long QT syndrome in pediatrics

Abstract

Long QT syndrome (LQTS) is an inherited heart disease responsible for serious arrhythmias. Identification of the mutation is essential for diagnosis, initiation of preventive treatment and family screening. The purpose is to evaluate the diagnostic yield of a panel of 21 genes in the pediatric revelation SQTL and secondarily to describe its clinical, paraclinical and therapeutic characteristics. Descriptive, retrospective and multicenter French study, conducted between 2015 and 2020, using genetic and clinical data from proband children analyzed with the same panel of genes in search of a LQTS. We included 366 patients, aged 11 [7] years, of which 47.5% had a causal mutation resulting mainly from the KCNQ1 (35.6%), KCNH2 (33.9%), SCN5A (14.9%) and including 37 unpublished variants. The genes in the level 2 panel represented 13.2% and the syndromic forms 8.6% of the mutations. Among the 151 patients with an available Schwartz score, 23.5% of patients with mutations had a low clinical probability. Finally, 69% of patients with clinical data collected ( n = 42) had symptoms and the main circumstances of discovery were syncope (45.2%), accidental discovery (28.6%) and cardio-respiratory arrest (9.5%). The genetic yield in the pediatric revealing LQTS is 47.5%. We describe a higher rate of mutations in the SCN5A gene, minor genes in the level 2 panel and syndromic forms, compared to data from the current literature. The poor performance of genetic diagnosis calls for further research, particularly with the growth of the whole genom sequencing.