Arrhythmias including Atrial Fibrillation and Congenital Heart Disease in Kleefstra Syndrome: a possible epigenetic link. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology Vasireddi, S. K., Draksler, T. Z., Bouman, A., Kummeling, J., Wheeler, M., Reuter, C., Srivastava, S., Harris, J., Fisher, P. G., Narayan, S. M., Wang, P. J., Badhwar, N., Kleefstra, T., Perez, M. V. 2024


BACKGROUND: Kleefstra syndrome (KS), often diagnosed in early childhood, is a rare genetic disorder due to haploinsufficiency of EHMT1 and is characterized by neuromuscular and intellectual developmental abnormalities. Although congenital heart disease (CHD) is common, the prevalence of arrhythmias and CHD subtypes in KS is unknown.METHODS: Inspired by a novel case series of KS patients with atrial tachyarrhythmias in the USA, we evaluate the two largest known KS registries for arrhythmias and CHD: Radboudumc (50 patients) based on health record review at Radboud University Medical Center in the Netherlands, and GenIDA (163 patients) based on world-wide surveys of patient families.RESULTS: Three KS patients (aged 17-25 years) presented with atrial tachyarrhythmias without manifest CHD. In the international KS registries, the median(IQR) age was considerably younger; GenIDA/Radboudumc at 10/13.5 (12/13) years respectively. Both registries had a 40% prevalence of cardiovascular abnormalities, the majority being CHD, including septal defects, vascular malformations, and valvular disease. Interestingly, 4 (8%) patients in the Radboudumc registry reported arrhythmias without CHD, including one AF, two with supraventricular tachycardias (SVTs), and one with non-sustained ventricular tachycardia. The GenIDA registry reported one patient with AF and another with chronic ectopic atrial tachycardia. In total, atrial tachyarrhythmias were noted in six young KS patients (6/213 or 3%) with at least four (3 AF and 1 AT) without structural heart disease.CONCLUSION: In addition to a high prevalence of CHD, evolving data reveals early-onset atrial tachyarrhythmias in young KS patients, including AF, even in the absence of structural heart disease.

View details for DOI 10.1093/europace/euae003

View details for PubMedID 38195854