Ventricular Tachycardia, Catecholaminergic Polymorphic, 3

Alternative Names

  • CPVT3
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WHO-ICD-10 version:2010

Diseases of the circulatory system

Other forms of heart disease

OMIM Number

614021

Mode of Inheritance

Autosomal recessive

Gene Map Locus

4q13.1

Description

Catecholaminergic Polymorphic Ventricular Tachycardia  (CPVT) 3 is a rare arrhythmic disorder characterised by the overlapping features of both CPVT and Long QT Syndrome (LQTS). Affected patients exhibit adrenergic ventricular tachycardia with high prevalence of cardiac arrest and sudden cardiac death. They also suffer from recurrent atrial tachycardia which can trigger ventricular arrhythmias. Interestingly, patients have normal or mildly prolonged QTc at baseline with a paradoxical QT increase during adrenergic stimulation.Arrhythmic episodes are usually induced by exertion or stress. Affected individuals can suffer such episodes in early childhood, often resulting in sudden death. While CPVT has an overall prevalence of 1 in 10,000 individuals, CPVT3 has only been reported in a handful of families thus far. The condition does not have a gender or racial bias.

The disorder can be diagnosed based on clinical features and genetic analysis of the TECRL gene. Early diagnosis and management of CPVT3 is crucial in preventing cardiac episodes. Treatment includes the use of beta-blockers, flecainide therapy and implantable cardioverter defibrillators (ICDs). Genetic counselling is also recommended for asymptomatic family members of affected individuals.  

Molecular Genetics

The disorder follows an autosomal recessive pattern of inheritance and is caused by mutations in the TECRL gene. This gene encodes an integral membrane protein with oxidoreductase activity. Knockdown of TECRL in human embryonic stem cell-derived cardiomyocytes results in significantly prolonged action potentials and reduced cell content of the canonical calcium-handling proteins RYR2 and CASQ2. Variants in TECRL associated with CPVT3 include a missense mutation (R196Q) and a splice-site mutation (c.331+1G-A). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the splice-site mutation have been found to exhibit electrophysiological and calcium-handling abnormalities as well as an increased susceptibility to triggered electrical activity upon catecholaminergic stimulation by noradrenaline.  

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
614021.1.1SudanMaleYesYes Cardiac arrest; Arrhythmia; Prolonged QT...NM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007
614021.1.2SudanMaleYesYes Sudden cardiac death; Syncope; Prolonged...NM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007 Brother of 614021.1....
614021.1.3SudanFemaleYesYes Sudden cardiac deathNM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007 Double first cousin ...
614021.1.4SudanMaleYesYes Death in childhood; Ventricular tachycar...NM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007 Double first cousin ...
614021.1.5SudanFemaleYesYes Sudden cardiac death; Ventricular septal...NM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007 Double first cousin ...
614021.1.6SudanMaleYesYes Ventricular arrhythmiaNM_001010874.5:c.331+1G>AHomozygousAutosomal, RecessiveDevalla et al. 2016; Bhuiyan et al, 2007 Double first cousin ...
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