PRKAG2 syndrome is a rare, autosomal dominant disease caused by mutations in the gene which encodes AMPK, a protein involved in regulation of glycogen metabolism. Clinical manifestations include ventricular pre-excitation, ventricular hypertrophy, atrial arrhythmias, conduction disorders, and sudden death.
This study describes the long-term clinical course, and incidence of cardiac complications in patients with PRKAG2 syndrome.
Observational, single-family study involving a cohort of PRKAG2 mutation carriers. Clinical, electrocardiographic, echocardiographic, and electrophysiology study findings were analyzed.
From March 1996 to January 2020, data were obtained from 16 related carriers of an Arg302Gln mutation in the PRKAG2 gene (10 males, mean age 40±11 years). Three individuals (18%) experienced sudden death. The prevalence of ventricular pre-excitation was 100%, right bundle branch block 69%, atrial flutter/atrial fibrillation 46%, and left ventricular hypertrophy 54%. Five patients (38%) received pacemakers (mean age 41 years). Electrophysiology study was performed in 6 patients and demonstrated fasciculoventricular accessory pathway; malignant arrhythmias could not be induced. The likelihood of sudden death or pacemaker implantation by age 40 was 44%. A significant association was observed between atrial flutter and need for pacemaker placement (P=0.032).
High prevalence of cardiac abnormalities was observed in a family with PRKAG2 syndrome secondary to Arg302Gln mutation. Affection by atrial flutter, third-degree atrioventricular block, and sudden death occurred at early ages, before 50 years. It is possible that the appearance of atrial flutter identifies patients most likely to have a pacemaker implant. However, this finding requires further evaluation in larger cohort studies.
© 2021 Published by Elsevier Inc.