Expanding the electrical phenotype of NKX2-5 mutations: Ventricular tachycardia, atrial fibrillation, and complete heart block within one family

NKX2-5 is a cardiac homeobox gene that is pivotal in the development of the myocardium and conduction system.1 Cardiac structural abnormalities and conduction disturbances have been described in the pediatric population with NKX2-5 mutations in recent years.2 Of the structural abnormalities, atrial septal defect (ASD) is the signature phenotype, although conotruncal defects, systemic and pulmonary outflow obstructions, and cardiomyopathies have also been reported.3, 4 Additionally, sudden death has been reported in patients with these mutations.5 Adult literature has demonstrated the presence of NKX2-5 mutations in patients with lone atrial fibrillation presenting in their early 40s.6 However, there are no current reports of patients with NKX2-5 mutations presenting with atrial fibrillation in teenage years or young adulthood. A recent study described the presence of ventricular tachycardia found incidentally on a pacemaker check in a patient with a strong family history of sudden death and NKX2-5 mutations.7 We previously published a paper describing a novel mutation in the NKX2-5 gene in a family with a history of sudden death.8 Our initial report described 2 male siblings with familial NKX2-5 mutation who had congenital heart defects, left ventricular noncompaction cardiomyopathy, and bradyarrhythmias as children. We now present an update on these 2 patients as young adults who went on to develop tachyarrhythmias prompting implantable cardioverter defibrillator (ICD) therapy, highlighting the importance of maintaining a high index of suspicion and considering increased surveillance for potentially dangerous rhythm abnormalities in this patient population.