Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

M.Sc. Alexander Moscu-Gregor, Dr. rer. nat. Christoph Marschall

Scientific Background

CPVT is an autosomal dominant inherited disease of structurally healthy heart muscle with an incidence of about 1:10,000. Adrenergic induction causes arrhythmias to manifest at an average age of 8 years old; bidirectional or polymorphic ventricular tachycardias are typical. Untreated, 60% of cases of CPVT lead to syncopes before the age of 40 and 30–50% to sudden cardiac death before the age of 30. A resting ECG appears normal. The earlier syncope occurs, the worse the prognosis and for men the risk of cardiac events is about four times higher. Beta blockers are used to treat the disease; however, approximately 30% of all patients remain symptomatic and may need an implantable defibrillator.

Causative mutations in the RYR2 gene (ryanodine type 2 receptor) can be identified in 40-70% of CPVT patients. This cardiac ryanodine receptor is the most important Ca++ releasing channel of the sarcoplasmic reticulum (SR) and plays a central role in the activation of cardiomyocytes. Around 3-5% of patients have detectable mutations in the CASQ2 (calsequestrin) and TECRL (trans-2,3-enoyl-CoA reductase-like) genes leading to an autosomal recessive inherited type of CPVT. Mutations in these three genes cause Ca++ to leak from the SR. Similar to mutations in the RYR1 gene, which are the cause of malignant hyperthermia, mutations in the RYR2 gene are most often located at the carboxy-terminal coding end of the gene.


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