Over the past decades, the knowledge of genetics has improved substantially and is becoming increasingly important in the understanding of diseases and development of individual-based treatment strategies. In cardiac electrophysiology, specific genetic mutations or subtypes are able to cause severe clinical arrhythmias leading to sudden cardiac death. Recently, a specific haplotype of the dipeptidyl-peptidase 6 (DPP6) gene was found to be associated with a risk of idiopathic ventricular fibrillation (VF). A single base transition in a regulatory region of the DPP6 gene results in an increased DPP6 expression. DPP6 is suggested to be a key element of the voltage-gated potassium channel, which contributes to the transient outward current (Ito). Recent findings propose an early repolarization syndrome in the Purkinje fibers as possible mechanism facilitating VF. In a Dutch cohort of idiopathic VF families, the high-risk haplotype was found in 20% and was associated with a 50% incidence of sudden cardiac events before the age of 58. Therefore, carriers of the risk haplotype of the DPP6 gene are currently advised an implantable cardioverter-defibrillator (ICD) for primary prevention between the ages of 20 and 50 years, in which there is an increased risk of sudden (cardiac) death. VF can also be triggered by various other conditions and medications and the cause determines the indication for an ICD. This case is the 1st to describe 2 separate episodes of VF in a DPP6 carrier above the indicated age for preventive ICD treatment. It represents the difficulties in determining the cause and indications for ICD and the manner in which genetic makeup will become increasingly important in determining treatment plans.

doi.org/10.1097/MAJ.0000000000000542, hdl.handle.net/1765/91038
American Journal of the Medical Sciences
Department of Cardiology