Cardiac channelopathies in pediatrics: a genetic update.

Abstract

Cardiac channelopathies are a group of inherited syndromes that can cause malignant arrhythmias and sudden cardiac death, particularly in the pediatric population. Today, a 12-lead electrocardiogram is the most effective tool to diagnose these diseases. Incomplete penetrance and variable expressivity are hallmarks of these syndromes. Some of these malignant entities may remain hidden and only a trigger such as exercise, emotions or fever can unmask the electrical pattern to diagnose the disease. Sudden cardiac death may be the first manifestation of any of these syndromes. The use of complementary tests that allow early diagnosis is strongly recommended, among which we find: pharmacological provocations, exercise tests, and genetic analysis. Genetic testing makes it possible to unravel the origin of the disease, and also identify family members who carry the harmful genetic defect and are therefore at risk. One of the main challenges in this area is the large number of genetic variants of uncertain significance, which prevent effective translation into clinical practice. Early identification of the pediatric population at risk and adequate risk stratification are crucial to adopting personalized preventive measures that reduce the risk of lethal episodes in this population. What is Known: • In the pediatric population, malignant arrhythmias leading to sudden cardiac death are mainly caused by inherited syndromes. • A conclusive genetic diagnosis unravels the origin of the syndrome and allows cascade screening to identify relatives carrying the genetic alteration. What is New: • The use of sequencing technologies allows a broad genetic analysis, helping to unravel new genetic alterations causing inherited arrhythmogenic syndromes. • A periodic reanalysis of genetic variants that currently have an ambiguous role will help discern those that are truly pathogenic.