Abstract
Background. Atrial fibrillation (AF) is a common arrhythmia in elderly patients and is associated with increased risk of mortality. The pathogenesis of AF is complex and based on multiple genetic and environmental factors. Genome-wide association studies identified several loci in AF patients, indicating the complex genetic architecture of this disease. In rare cases, familial forms of AF have been described. Today, pathogenic variants in at least 11 different genes are associated with monogenic AF. Case presentation. The 37-year-old male patient presented to our emergency department with AF. At the age of 35, he had already been diagnosed with paroxysmal AF. Additionally, his 34-year-old brother had also been diagnosed with AF as well as nonobstructive hypertrophic cardiomyopathy. Moreover, the patient's father was diagnosed with AF in his twenties. Transthoracic echocardiography and cardiac MRI revealed a reduced systolic left ventricular ejection without any signs of hypertrophic cardiomyopathy. Genetic testing identified the heterozygous missense variants c.3371C > T, p.(Pro1124Leu) in RYR2 (NM_001035.3) and c.2524C > A, p.(Pro842Thr) in HCN4 (NM_005477.3) in the patient's and his brother's DNA. Discussion. This case of familial AF helps to strengthen the role of RYR2 as a disease gene in the context of AF. Although the variant in RYR2 needs to be classified formally as variant of unknown significance, we regard it as probably disease-causing due to the previously published data. As RYR2 has already been identified as a possible target for prevention and therapy of AF, the knowledge of variants in RYR2 might become even more crucial for individual molecular therapies in the future.