CASQ2: clinical and genetic insights into catecholaminergic polymorphic ventricular tachycardia across three families

Catecholaminergic polymorphic ventricular tachycardia is a primary channelopathy with a high mortality rate if left untreated. In 3 to 5% of catecholaminergic polymorphic ventricular tachycardia patients, mutations in the CASQ2 gene, either in a homozygous or compound heterozygous form, have been identified. In this article, we present a clinical case series of patients from three unrelated families with mutations in the CASQ2 gene, including three novel mutations (p.Leu167Pro, p.Asp325GlyfsTer7, and p.Glu259Ter). All our patients with homozygous or compound heterozygous CASQ2 gene mutations experienced a severe disease course, with early manifestations and resistance to specific anti-arrhythmic treatment, including beta-blockers. They exhibited a wide range of heart rhythm abnormalities, both ventricular and supraventricular, and had a high risk of sudden cardiac death. In all cases, ventricular heart arrhythmias persisted despite regular treatment with specific anti-arrhythmic agents, unless selective left-sided sympathectomy had been performed. The management of this patient group emphasized an individualized approach, combining medical and surgical treatment methods tailored to each patient's unique needs and condition.