# Cardiac arrhythmias and genetics – current stage

## TL;DR

This paper reviews the current understanding of inherited cardiac arrhythmias, their genetic basis, and the role of genotyping in diagnosis and prevention.

## Contribution

The paper provides an updated overview of genetic aspects and clinical guidelines for diagnosing and managing inherited cardiac arrhythmias.

## Key findings

- Inherited cardiac arrhythmias are rare and often autosomal dominant, with genetic heterogeneity and variant detection rates between 10% and 80%.
- Genotyping helps in early disease recognition and prevention of severe cardiac events, supported by current clinical guidelines.
- Environmental triggers and additional genetic or non-genetic modifiers influence the clinical expression of these disorders.

## Abstract

Recently, cardiogenetics is a rapidly developing medical section combining cardiovascular and genetic knowledge. Inherited forms of cardiac arrhythmias are typically rare diseases (prevalence < 1:2,000) and may occur in a sporadic or familial manner, here mostly in an autosomal dominant form. They are also called “primary electrical heart disorders” due to the ECG-based diagnosis and mainly normal cardiac imaging, i.e. absence of structural heart abnormalities. Their genetic basis is heterogeneous, still incomplete (variant detection rates between 10 % and 80 %) and mostly related to cardiac ion channel genes and related regulatory units. So far, the utility of polygenic risk scores is under current evaluation. Clinical disease expressivity may range from non-penetrance to high penetrance, indicating the importance of additional clinical modifiers (genetic and non-genetic) that modulate phenotypic signs. Occurrence of symptoms, as typical for other ion channel disorders (e.g., epilepsy), also depends on exposure to specific and often genotype-related environmental triggers, that enhance the occurrence of clinically relevant and potentially life-threatening arrhythmias.

In the following, the main focus is on cardiac ion channel disorders, with regard to some general genetic aspects and current guidelines indicating the value of genotyping to support early disease recognition, confirmation of diagnosis and prevention of severe cardiac events.