CLINICAL AND MOLECULAR GENETIC BASIS OF SUDDEN CARDIAC DEATH IN CHILDREN WITH PRIMARY ELECTRICAL HEART DISEASES (PEHDS)
Authors:   Research and Clinical Institute of Pediatrics named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Shkolnikova M.A. , Ildarova R.A. ,   Research and Clinical Institute of Pediatrics named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia, Shcherbakova N.V. ,   Research and Clinical Institute of Pediatrics named after Academician Yuri Veltischev with the Pirogov Russian National Research Medical University, Moscow, Russia
Published: May 2022

Primary electrical heart diseases (PEHDs) are hereditary orphan life-threatening conditions leading to a sudden cardiac death in young adults in the absence of structural heart disease. Among the most common and studied diseases of this group are: long QT syndrome (LQTS), catecholaminergic ventricular tachycardia, Brugada syndrome, short QT syndrome, early ventricular repolarization syndrome. Also, this group of diseases includes congenital sick sinus syndrome, progressive cardiac conduction defect, idiopathic ventricular fibrillation, familial atrial fibrillation and a number of cases (from 5 to 10%) of the sudden cardiac death syndrome in infants. The total prevalence of PEHDs in the pediatric population is quite high and is about 1:2000, mainly due to long QT syndrome. PEHDs are poorly identified by the standard clinical approach, at the same time a delay in diagnosing and prescribing specific therapy may lead to fatal consequences and sudden cardiac death of the child at the first-ever syncope. The vast majority of PEHDs genes identified to date encode subunits of cardiac ion channels or proteins, which interact with ion channels and regulate their functions. The advent of the next generation sequencing led to a shift in most DNA diagnostics laboratories from screening single genes or small gene panels to examining of whole exome or whole genome data. These diseases, especially LQTS, have become unique cardiological models for clinical and genetic studies, analysis of genotype-phenotype correlations and the development of a modern strategy of multi-level hybrid therapy and the prevention of sudden cardiac death (SCD) in people of young age. The most PEHDs can and should be diagnosed in childhood, which now makes it possible to effectively prevent life-threatening arrhythmias. More and more patients are surviving into adulthood, as yet, and patients are interacting with traditional risk factors and obviously should have higher cardiovascular risks. Due to the high prevalence in the population, the association with the SCD, the polymorphism of clinical and genetic manifestations, high technology medicine, the research of PEHDs has become one of the priority places in both pediatric and adult cardiology, and the diseases have now become models for development of gene therapies. The paper outlines the clinical and genetic characteristics, the basics of diagnostics and up-to-date therapeutic, interventional and surgical technologies for the treatment of the most common PEHDs in childhood.