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

Background

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).

Objective

In the Northern Ireland pediatric 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.

Methods

Retrospective chart review using the local pediatric cardiology database.

Results

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 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 %.

Conclusions

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.