PO98 Sudden cardiac arrest: the hidden genetic danger

Abstract Sudden cardiac arrest (SCA) in young adults is a tragic event, and a thorough investigation of its underlying causes is essential to prevent future occurrences. A high index of suspicion is needed when evaluating these patients, with particular attention to red flags. We report the case of a 26-year-old man with Wolff-Parkinson-White (WPW) syndrome, diagnosed at age 12, and paroxysmal atrial fibrillation (AF). He was on daily treatment with propafenone and bisoprolol. He was brought to the emergency department following successful resuscitation from SCA in ventricular fibrillation while at rest. The first electrocardiogram after resuscitation showed AF with aberrant conduction. Pharmacological cardioversion was performed, restoring sinus rhythm, with short PR interval and delta wave consistent with ventricular pre-excitation (Figure 1). The echocardiogram revealed interventricular septal (IVS) hypertrophy (21 mm), with no additional abnormalities. During hospitalization, a significant family history was unveiled. His mother had been diagnosed with PRKAG2 syndrome. She presented with left ventricle hypertrophy (LVH), WPW syndrome, AF, and had pacemaker implantation at age 41 due to complete atrioventricular block (AVB). His maternal uncle also had LVH, AF, pacemaker implantation at age 33 due to AVB and performed an upgrade to implantable cardioverter-defibrillator (ICD) at age 39 following syncope associated with palpitations. His grandfather, who passed away at 77 years old, also had AF, IVS hypertrophy with reduced LV ejection fraction and had a pacemaker implantation at age 39 for complete AVB. Cardiac magnetic resonance imaging revealed findings compatible with non-obstructive hypertrophic cardiomyopathy, with a maximum wall thickness of 20–21 mm in the mid-segment of the inferior septum, with midwall late gadolinium enhancement in the same segment The patient underwent successful catheter ablation of the accessory pathway and ICD implantation for secondary prevention. Genetic testing identified a missense mutation in exon 7 of the PRKAG2 gene (c.905 G>A p.(Arg302Gln), the same pathogenic variant found in his mother. Relatives’ cascade screening confirmed the PRKAG2 syndrome diagnosis of his maternal uncle and the identification of the same mutation in his cousin, who is now being followed in the Cardiomyopathy Consultation (with no phenotype so far). PRKAG2 syndrome is a rare autosomal dominant disease, with an incidence of premature SCA reaching up to 20%. Most reported PRKAG2 gene variants are missense mutations. It potentially leads to a classical triad: LVH, ventricular pre-excitation, and premature conduction system disease. This case highlights the critical role of thorough family history assessment in young patients who present with SCA, and the value of genetic screening in hereditary cardiac disorders.