Description of a novel RyR2 mutation in a juvenile patient with symptomatic catecholaminergic polymorphic ventricular tachycardia in sleep and during exercise: a case report

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an inherited disease presenting with arrhythmic events during physical exercise or emotional stress. If untreated, catecholaminergic polymorphic ventricular tachycardia is a highly lethal condition: About 80% of affected individuals experience recurrent syncope, and 30% experience cardiac arrest. Catecholaminergic polymorphic ventricular tachycardia is caused by mutations in genes encoding ryanodine receptor type 2 (RyR2) and cardiac calsequestrin (CASQ2). In cases of sympathoadrenergic activation, both mutations result in a spontaneous Ca(2+) release in cardiac cells, facilitating ventricular arrhythmias. CASE PRESENTATION: We present a case of a 17-year-old Caucasian boy who survived sudden cardiac death caused by ventricular fibrillation while performing running exercise in a fitness center. The diagnostic workup included blood tests, coronary angiography, electrophysiological testing, and cardiac magnetic resonance imaging, but all results were normal. Because the patient’s medical history included recurrent syncope during physical and emotional stress, we strongly suspected catecholaminergic polymorphic ventricular tachycardia as the underlying disease. Genetic screening was performed and confirmed the diagnosis, revealing a new heterozygous point mutation in the gene for RyR2, c.12520T>A (p.F4174 l, exon 90, RyR2 gene). The patient was discharged from our hospital after undergoing implantation of an implantable cardioverter defibrillator for secondary prevention. Shortly after implantation, the implantable cardioverter defibrillator terminated a sustaining ventricular tachycardia episode by antitachycardic pacing. This episode occurred early in the morning while the patient was asleep. CONCLUSIONS: We present a case of catecholaminergic polymorphic ventricular tachycardia associated with a novel single point mutation in the RyR2 gene, which, to the best of our knowledge, has not been described in the literature so far. Our patient experienced arrhythmic events under both resting conditions and physical activity, an uncommon finding in patients with catecholaminergic polymorphic ventricular tachycardia. This novel mutation may cause arrhythmias independent of sympathoadrenergic stimulation, but further evidence is needed to prove causality.