1265The results of whole exome sequencing in patients with bradyarrhythmias

Abstract

Abstract Introduction. Sick sinus syndrome (SSS) and atrioventricular block (AVB) are life-threatening cardiac arrhythmias, that sometimes can manifest itself with syncope and needs a pacemaker implantation even in children. Sometimes, SSS and AVB are accompanied by structural heart diseases such as septal defects, cardiomyopathies, but often the heart is structurally normal. Some genes associated with bradyarrhythmias are well known. At the same time, the etiology of the SSS is unidentified and may be genetic caused in 50% of patients with SSS. There are no studies on the prevalence of with bradyarrhythmia-associated mutations in children. The purpose of our work is to identify and study the types of mutations associated with SSS and AVB in children. Methods. We included in the study 15 patients (27% boys) with severe SSS and AVB, from the database of the Russian Pediatric Arrhythmia Center. 11 were the probands and 4 - family members. Personal and family history, physical examination, including ECG, stress test, Holter monitoring, ECHO and other tests, and whole exome sequencing were made. The average age was 14.1 ± 4.5 (from 2 to 17). Results. In 30% (5 pts) there was the combination of with bradyarrhythmias and structural heart disease. 7 pts (47%) had syncope, 4 pacemakers were implanted. 10 children (67%) had the genetic variants of genes associated with SSS and AVB: SCN5A, TNNI3K, KCNA5, TRPM4, ANK2 and others. Family history of cardiac diseases was positive in 5 probands; 2 probands had family members with implanted pacemakers. In 3 pts were likely pathogenic variants and in 7 pts - variants of unknown significance found. Conclusion. We found the genetic cause of bradyarrhythmias in 67% of children. Further research and larger patient samples are required to study the prevalence of genetic types of and show the correlation of the genotype with the clinical prognosis. In addition, our work will enable practitioners to identify children from families with family forms of SSS, AVB and sudden cardiac death. Further research can help us determine the criteria for selecting children for genetic testing.