PRKAG2 Syndrome: Clinical Features, Imaging Findings and Cardiac Events.

Area of Science:

• Cardiology
• Genetics
• Rare Diseases

Background:

• PRKAG2 syndrome (PS) is a rare genetic disorder mimicking hypertrophic cardiomyopathy (HCM).
• Limited data exists on the clinical spectrum and long-term outcomes of PS patients.
• Understanding PS is crucial for accurate diagnosis and management.

Purpose of the Study:

• To expand the understanding of PRKAG2 syndrome by analyzing clinical, imaging, and follow-up data.
• To characterize the phenotype and genotype correlations in PS.
• To identify key cardiac events and outcomes in PS carriers.

Main Methods:

• Retrospective analysis of seven patients with pathogenic PRKAG2 variants (2011-2022).
• Cardiac assessment included ECG, echocardiography, cardiac MRI, and endomyocardial biopsy (EMB).
• Clinical data, concomitant diseases, and cardiac events were systematically recorded.

Main Results:

• Five of seven patients exhibited left ventricular hypertrophy (LVH); arrhythmias like ventricular pre-excitation and atrial flutter were observed.
• EMB revealed glycogen deposits in one patient and linked the Val336Leu PRKAG2 variant to autophagy.
• Over a median 13.1-year follow-up, 6 carriers had LVH, 3 were admitted for heart failure (HF), and one experienced sudden cardiac death.

Conclusions:

• PRKAG2 syndrome is a distinct condition characterized by early-onset arrhythmias.
• The syndrome frequently progresses to heart failure and carries a risk of sudden cardiac death.
• Comprehensive cardiac evaluation and long-term monitoring are essential for PS management.