Identifying PRKAG2 syndrome—a rare cause of wolff-Parkinson-white syndrome and left ventricular hypertrophy: a case report

In young patients presenting with Wolff-Parkinson-White syndrome and left ventricular hypertrophy (LVH), a genetic aetiology should be considered, particularly when cardiovascular risk factors such as hypertension or valvular heart disease are not present, or when there is a suggestive family history of cardiomyopathy. PRKAG2 syndrome is a rare genetic disorder characterized by cardiac glycogen storage, ventricular pre-excitation, and hypertrophy, often mimicking hypertrophic cardiomyopathy (HCM).

A 22-year-old male with a history of WPW syndrome presented with recurrent palpitations and wide QRS tachycardia. Post-cardioversion electrocardiography (ECG) revealed persistent pre-excitation, and transthoracic echocardiography confirmed LVH with preserved systolic function. Cardiac magnetic resonance imaging demonstrated normal myocardial mass without late gadolinium enhancement. Genetic testing, prompted by a family history of sudden cardiac death (SCD), using a targeted panel sequencing including sarcomere protein gene mutations and other cardiomyopathy-related genes, identified a heterozygous PRKAG2 mutation. Given the high-risk of SCD, implantable cardioverter-defibrillator placement was recommended but declined. The patient subsequently experienced a fatal cardiac arrest 8 days after the last clinic visit.

This case highlights the importance of genetic evaluation in young patients with unexplained arrhythmias and hypertrophy. PRKAG2 mutations, often overlooked in standard HCM panels, can lead to misdiagnosis and inadequate risk stratification. Clinicians should maintain a high index of suspicion for PRKAG2 syndrome, particularly in patients with conduction abnormalities, ventricular arrhythmias, and LVH. Early identification using genetic tests, risk assessment, and family screening are crucial to preventing adverse outcomes, including SCD.