Current topics of inherited arrhythmias

Inherited arrhythmia syndromes are genetically determined disorders of cardiac ion channels or ion channel macromolecular complexes that predispose affected individuals to sudden cardiac death. During the last two decades, evolving knowledge on the genetic basis of inherited arrhythmia has dramatically broaden our understanding of these conditions and, consequently, provided a great impact on patient care. Numbers of investigations have launched to develop a gene- and even mutation-specific therapy in monogenetic inherited arrhythmias such as long QT syndrome.　However, such gene-disease association is ill-defined in other inherited arrhythmias, and, in fact, it has become evident that the genetic architectures of inherited arrhythmias are more complex than previously thought, involving more genetic components than a single gene locus. The high-throughput next generation sequencing (NGS) is a revolutionized genome research technology that allows us to uncover disease-causing new variants/mutations. However, NGS has disclosed unexpectedly high rate of background genetic variations whose association with disease risk is unknown. To confirm pathogenicity of these variations and improve the state of diagnosis of genetic testing, a number of criteria is required to be carefully evaluated with multidisciplinary approaches by experts in the field including geneticists, cardiologists, and genetic counselors. These efforts will allow the findings of genetic testing to be interpreted in the context of clinical practice. In this symposium, we will discuss the current advancements and the challenges we face in inherited arrhythmia by focusing on its clinical, genetic, genomic, and pathophysiological aspects.