Early recognition of PRKAG2 syndrome in an adolescent with a hypertrophic cardiomyopathy phenotype and ventricular pre-excitation: a case report

Abstract

PRKAG2 syndrome is a rare glycogen-storage cardiomyopathy that can mimic sarcomeric hypertrophic cardiomyopathy (HCM). The diagnostic clue is not left ventricular hypertrophy alone, but the combination of hypertrophy with ventricular pre-excitation and conduction-system abnormalities. This pattern is clinically important because PRKAG2 syndrome differs from sarcomeric HCM in disease progression, arrhythmic risk, and long-term management. A 12-year-old boy presented with recurrent exertional chest tightness. Twelve-lead electrocardiography showed ventricular pre-excitation, and echocardiography demonstrated asymmetric non-obstructive left ventricular hypertrophy. An external Holter report recorded sinus bradycardia and nocturnal pauses. Genetic testing identified a heterozygous PRKAG2 variant, NM_016203:c.1423A>G (p.Lys475Glu), classified as likely pathogenic. The available report from a clinically indicated invasive electrophysiological procedure documented persistent pre-excitation and localized the earliest antegrade ventricular activation to the right midseptal para-Hisian region. Catheter ablation was deferred because no tachyarrhythmia had been documented and ablation near the His bundle carried a substantial risk of atrioventricular block. During approximately 2 years of follow-up, the patient remained clinically stable, with persistent hypertrophy and no major arrhythmic or conduction events. In adolescents with otherwise unexplained ventricular hypertrophy, ventricular pre-excitation should prompt consideration of PRKAG2 syndrome and other HCM phenocopies, even without a positive family history. Recognition of this combined structural and electrical phenotype may facilitate earlier genetic diagnosis and guide long-term rhythm surveillance. The mechanism of pre-excitation should be described only to the extent supported by the available electrocardiographic and procedural documentation.