Cardiac arrhythmias constitute one of the main causes of morbidity and mortality. Congenital cardiac arrhythmias are a separate group of heart disorders resulting from defects in the electro-physiological properties of the heart. Specifically, coordination of cardiac activity includes, among other, the synchronous and sequential opening and closing of ion channels in response to the electrical potential and subsequent transmission of the action potential to each compartment of the heart.
Although environmental factors clearly contribute to arrhythmogenesis, family and population studies have also demonstrated an underlying genetic etiology. For example, mutations in >20 genes, which encode and/or modulate specific ion-channels, are associated with various forms of arrhythmias, occurring in an otherwise structurally normal heart.
As an example, Brugada Syndrome (BRS), is associated with mutations in at least seven different genes and is characterized by an increased risk of fatal ventricular arrhythmias. Sudden cardiac death (SCD), or sudden unexplained death, is a common cause of mortality, affecting all ages. The primary cause of sudden cardiac death in people older than 45 years is mainly due to atherosclerotic coronary artery disease. However, in individuals <45 years, genetic and hereditary defects in specific genes have been associated with the disease in up to 80% of cases.
Generally, the majority of heart diseases associated with arrhythmias are expressed and inherited in an autosomal dominant manner, which means that individuals with a mutation in only one of the two copies of a gene have a particularly high risk of manifesting the disease and all first-degree relatives of a patient have a 50% risk of inheriting the disease. It is also important to bear in mind that different mutations in the same gene can lead to the expression of different types of a cardiogenetic disease.