Channelopathies in children in Northern Ireland 2005–2023: A national cohort study identified primarily via cascade screening

The inherited cardiac channelopathies are a diverse range of conditions caused by genetic variants that predispose carriers to arrhythmia and sudden cardiac death (SCD). Examples include Congenital Long QTc (LQTS), Brugada syndrome (BrS) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). In the Northern Ireland paediatric population, served by one inherited cardiac conditions clinic (ICCC) we describe the national prevalence and incidence of the channelopathies, clinical outcomes, adverse events, medication usage, medication adherence and genetic data obtained. Retrospective chart review using the local paediatric cardiology database. 216 children (Aged 0–18) were diagnosed with a channelopathy between 2005 and 2023 at the ICCC; 190 were diagnosed with LQTS (116 KCNQ1, 36 KCNH2, 11 SCN5A, 19 KCNE1, 3 patients with variants in two genes, 1 compound heterozygote for KCNE1 and 4 genotype negative), 22 with BrS and 4 with CPVT. Most cases were diagnosed via screening (95 %). There were five documented SCDs during this time, all patients unknown to the ICCC, who were diagnosed with channelopathies on molecular autopsy (2 CPVT, 2 BrS, 1 LQTS). One KCNH2 patient underwent implantable cardioverter defibrillator (ICD) insertion. In the LQTS cohort the majority had a variant identified (97 %) Twenty-two variants were identified in KCNQ1 patients, fourteen variants in KCNH2, two in SCN5A and seven in KCNE1. As would be expected phenotype heterogeneity was noted between and within variants. Adherence with medication varied between 70 and 90 %. In general, children with channelopathies in Northern Ireland (NI) are diagnosed via family screening, commenced on appropriate pharmacotherapy and adverse events are rare. The genetic profile is broadly similar to that reported worldwide. Unfortunately, there remains a cohort of patients who are only identified at molecular autopsy. • Comprehensive study examining diagnosis, follow-up, management and BCE rate of all known children with ICCs • Prevalence of LQT 1 in 2500, Prevalence of BrS 1 in 22,000 for NI • Very few BCEs in patients known to clinic, 5 SCDS as presentation in examined period. • Generally high adherence in this group of patients • Comprehensive genetic variant data; similar profile to worldwide reports.