Clinical Spectrum of PRKAG2 Syndrome.

Abstract

PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant inherited disease, characterized by ventricular pre-excitation, supraventricular arrhythmias, and cardiac hypertrophy. It is frequently accompanied by chronotropic incompetence and advanced heart blocks, leading to premature pacemaker implantation. The association of these clinical features had previously been recognized by several studies since the second half of the 20th century.1–3 In 1991, PRKAG2 syndrome was mapped to the locus 7q 36,4 and in 2001, Gollob et al5 identified the responsible gene. The syndrome is caused by mutations in the gene encoding for the 5′ AMP-activated protein kinase (AMPK), specifically for its γ2 regulatory subunit (PRKAG2). AMPK is an enzyme deeply involved in cellular ATP metabolic regulation.6 PRKAG2 genetic mutations are rare and have been recognized mainly in the context of patients with nonsarcomeric familial hypertrophic cardiomyopathy associated with Wolff–Parkinson–White syndrome.7 PS can show different expressivity both of ventricular hypertrophy and arrhythmic features, ranging from an asymptomatic condition to sudden cardiac death (SCD). PS can occasionally lead to heart failure (HF) or demonstrate systemic involvement.7–9 This review aims to describe the various features and clinical implications of PS, providing clinicians and researchers with a summary of the published literature to improve the diagnosis and to better manage the clinical course of the disease. A search of the English literature was performed using PubMed up to September 2014 on the clinical features, genetics, and pathophysiology of PS syndrome. The term PRKAG2 combined with either cardiomyopathy, Wolff–Parkinson–White syndrome, atrial fibrillation, familial, left ventricular hypertrophy, atrioventricular (AV) block, pacemaker, SCD, HF, clinical characteristics, genotype, phenotype, or mutations was used. Observational studies, case reports, and reviews were included in our search. References were carefully evaluated for …