953 KEY ROLE OF GENETIC ANALYSIS IN A FAMILIAR CASE OF HYPERTROPHIC CARDIAC PHENOTYPE AND VENTRICULAR PREEXCITATION RELATED TO PRKAG2 GENE MUTATION. (15th December 2022) - Scimé, Irene
Abstract: A 38-year-old male patient (A2) was referred to our ambulatory for paroxysmal atrial fibrillation in young age and ventricular preexcitation. Echocardiographic evaluation showed left ventricle hypertrophy (localized particularly at inter-ventricular septum (SIV) and normal LV ejection fraction. He also had a positive family history of hypertrophic cardiomyopathy since the latter was already diagnosed with the maternal grandmother (M0), the mother (M1) and the two brothers (A1 and A3). His father was apparently healthy (P1- consanguineous third degree of the mother M1). Specifically, the mother (M1) was suffering from non-obstructive hypertrophic cardiomyopathy, and tachy-brady (paroxysmal atrial flutter, sinus arrest) syndrome requiring pacemaker implantation. The firstborn (A1) was affected by paroxysmal atrial fibrillation, ventricular prexcitation and mild hypertrophy of the interventricular septum (SIV). The third child (A3) had a diagnosis of hypertrophic cardiomyopathy and a history of successfully ablation of a left postero-septal accessory pathway. A3 suffered also by paroxysmal typical atrial common flutter. Genetic analysis of the proband A2 confirmed a heterozygous pathological mutation of the PRKAG2 gene. Thus, genetic analysis was extended to the other two brothers A1 and A3 and the mother. We proposed to the all three brothers electrophysiological study in order to assess arrhythmic substrate and appropriate therapy (strict FUP, PM or ICD implantation). Mutation of the PRKAG2 gene is a rare disease, classified as non-lysosomal cardiac glycogenosis with clinical onset in late adolescence or in the third decade of life and presents an autosomal dominant inheritance with complete penetrance. It is associated with cardiac arrhythmias, such as ventricular preexcitation (Wolff-Parkinson-White syndrome), sinus node disease, atrioventricular block, atrial fibrillation. Genetic analysis has a crucial role especially in the evaluation of inheritance with autosomal dominant transmission and regarding the prognostic impact, since PRKAG2 gene mutation involved a greater arrhythmic risk comparing with other subtypes of hypertrophic cardiomyopathy. Affected patients should be closely monitored to facilitate early detection of arrhythmia and conduction problems. PRKAG2 mutation should be considered in patients with LVH who develop AF or require permanent pacemakers at a young age. Early recognition is important to allow prompt identification and appropriate management of genetic carriers.