PO72 From Pre-Excitation to Complete AV Block with Ventricular Hypertrophy: A Case of PRKAG2 Syndrome

Introduction PRKAG2 syndrome is a rare autosomal dominant genetic disorder caused by mutations in the PRKAG2 gene, which encodes the γ2 subunit of AMP-activated protein kinase (AMPK). This mutation results in glycogen accumulation in cardiomyocytes and may clinically mimic sarcomeric hypertrophic cardiomyopathy (HCM). It is characterized by ventricular pre-excitation, supraventricular tachyarrhythmias, progressive atrioventricular (AV) block, and in advanced stages, heart failure. This case highlights the importance of early recognition of this entity in the differential diagnosis of HCM, particularly in the presence of early-onset AV block and Wolff-Parkinson-White (WPW) pattern. Case Report A 38-year-old independent man with a known WPW pattern on a prior ECG (who previously declined an electrophysiological study) was admitted on August 11, 2017, after experiencing a syncopal episode preceded by dizziness. Family history is notable for HCM and conduction disease: his mother had HCM and AV block requiring a pacemaker at 48, and his maternal grandfather also required a pacemaker. Pre-hospital ECG revealed complete AV block with a wide QRS escape rhythm (∼25 bpm). Echocardiography showed apical HCM and right ventricular hypertrophy. A dual-chamber permanent pacemaker was implanted without complications following temporary pacing. Genetic testing revealed a pathogenic PRKAG2 mutation (Arg302Gln). Family members declined cascade screening. The patient remained asymptomatic on follow-up. In 2025, pacemaker follow-up documented persistent atrial flutter with 100% right ventricular pacing. Echocardiogram showed moderate concentric LV hypertrophy (basal and mid segments) and severe apical thickening, with preserved biventricular systolic function. Oral anticoagulation was initiated. Discussion The triad of ventricular hypertrophy, AV block, and pre-excitation in a young adult with suggestive family history is highly indicative of PRKAG2 syndrome. Given the potential for severe complications like sudden cardiac death, early diagnosis through genetic testing is essential to distinguish it from sarcomeric HCM and to guide family screening, follow-up and prognosis.