Sudden death associated with a novel H401Q PRKAG2 mutation

PRKAG2 cardiomyopathy is a rare, autosomal dominant inherited disorder resulting from mutations in the gene encoding the γ2 regulatory subunit of AMP-activated protein kinase. Clinical manifestations include cardiac hypertrophy, ventricular preexcitation, atrioventricular conduction abnormalities, and atrial flutter and fibrillation. Its precise prevalence is challenging to define, due to phenotypic overlap on imaging with sarcomeric hypertrophic cardiomyopathy. Eighteen mutations have been reported to this date, most commonly Arg302Gln and Asn488Ile, constituting 57% and 21% of ∼270 reported cases, respectively. Greater clinical awareness of PRKAG2 cardiomyopathy is important given that both prognosis and management are distinct from familial hypertrophic cardiomyopathy. For patients bearing the most frequently mutation (Arg302Gln), clinical presentation is usually during the second decade of life. Sudden cardiac death may occur before 30 years, caused by atrial fibrillation conducting with rapid ventricular rate, or later, caused by atrioventricular block. We report a new missense PRKAG2 mutation (His401Gln) (Figure) in three of five family members, with a phenotype characterized by an early-onset of LVH, pre-excitation, atrial tachyarrhythmias, sinus bradycardia, and a high incidence of unexpected sudden cardiac death at a young age, probably caused by pre-excited atrial fibrillation with very fast ventricular rate. The full-length version of this report can be viewed at: https://www.escardio.org/Education/E-Learning/Clinical-cases/Electrophysiology.