Background: PRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood. Objectives: The aim of this study was to describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort. Methods: Clinical, electrocardiographic, and echocardiographic data from 90 subjects with PRKAG2 variants (53% men; median age 33 years; interquartile range [IQR]: 15 to 50 years) recruited from 27 centers were retrospectively studied. Results: At first evaluation, 93% of patients were in New York Heart Association functional class I or II. Maximum left ventricular wall thickness was 18 ± 8 mm, and left ventricular ejection fraction was 61 ± 12%. Left ventricular hypertrophy (LVH) was present in 60 subjects (67%) at baseline. Thirty patients (33%) had ventricular pre-excitation or had undergone accessory pathway ablation; 17 (19%) had pacemakers (median age at implantation 36 years; IQR: 27 to 46 years), and 16 (18%) had atrial fibrillation (median age 43 years; IQR: 31 to 54 years). After a median follow-up period of 6 years (IQR: 2.3 to 13.9 years), 71% of subjects had LVH, 29% had AF, 21% required de novo pacemakers (median age at implantation 37 years; IQR: 29 to 48 years), 14% required admission for heart failure, 8% experienced sudden cardiac death or equivalent, 4% required heart transplantation, and 13% died. Conclusions: PRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of atrial fibrillation, conduction disease, advanced heart failure, and life-threatening arrhythmias. Classical features of pre-excitation and severe LVH are not uniformly present, and diagnosis should be considered in patients with LVH who develop atrial fibrillation or require permanent pacemakers at a young age.

Original languageEnglish
Pages (from-to)186-197
Number of pages12
JournalJournal of the American College of Cardiology
Issue number2
StatePublished - 14 Jul 2020


FundersFunder number
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Fondazione per la Ricerca Ospedale Maggiore
Obra Social La Caixa Foundation100010434
Royal Brompton Cardiovascular Biomedical Research Unit
Spanish Ministry of Economy and Competitiveness
St. Bartholomew's Hospital
UCL Hospitals NIHR Biomedical Research Centre
Wellcome Trust107469/Z/15/
National Institute for Health Research
British Heart FoundationSP/10/10/28431
Department of Health and Social Care
Great Ormond Street Hospital Charity
Ministerio de Economía y Competitividad
Department of Health, Australian GovernmentHICF-R6-373
Instituto de Salud Carlos IIIPI17/01941, PI18/01582, AC16/0014, PI17/01690, PT17/0015/0043
European Regional Development Fund
Fondazione per la Ricerca Biomedica
Fundació Privada Daniel Bravo Andreu
NIHR Imperial Biomedical Research Centre
NIHR Great Ormond Street Hospital Biomedical Research Centre


    • PRKAG2
    • glycogen-storage disease
    • heart failure
    • hypertrophic cardiomyopathy
    • left ventricular hypertrophy
    • pacemaker
    • pre-excitation
    • sudden cardiac death


    Dive into the research topics of 'Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis'. Together they form a unique fingerprint.

    Cite this