Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death

Abstract Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to cause these conditions, but evidence supporting these gene–disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT and SQTS patients, we applied an evidence-based reappraisal of previously reported genes. Methods and results Three teams independently curated all published evidence for 11 CPVT and 9 SQTS implicated genes using the ClinGen gene curation framework. The results were reviewed by a Channelopathy Expert Panel who provided the final classifications. Seven genes had definitive to moderate evidence for disease causation in CPVT, with either autosomal dominant (RYR2, CALM1, CALM2, CALM3) or autosomal recessive (CASQ2, TRDN, TECRL) inheritance. Three of the four disputed genes for CPVT (KCNJ2, PKP2, SCN5A) were deemed by the Expert Panel to be reported for phenotypes that were not representative of CPVT, while reported variants in a fourth gene (ANK2) were too common in the population to be disease-causing. For SQTS, only one gene (KCNH2) was classified as definitive, with three others (KCNQ1, KCNJ2, SLC4A3) having strong to moderate evidence. The majority of genetic evidence for SQTS genes was derived from very few variants (five in KCNJ2, two in KCNH2, one in KCNQ1/SLC4A3). Conclusions Seven CPVT and four SQTS genes have valid evidence for disease causation and should be included in genetic testing panels. Additional genes associated with conditions that may mimic clinical features of CPVT/SQTS have potential utility for differential diagnosis.

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GENETIC REASONS OF SUDDEN CARDIAC DEATH

Vestnik of Russian military medical Academy ◽

10.17816/brmma12170 ◽

2017 ◽

Vol 19 (2) ◽

pp. 15-22

Author(s):

S N Kolyubaeva

Keyword(s):

Ventricular Tachycardia ◽

Sudden Cardiac Death ◽

Long Qt Syndrome ◽

Brugada Syndrome ◽

Cardiac Death ◽

Polymorphic Ventricular Tachycardia ◽

Normal Heart ◽

Short Qt Syndrome ◽

Long Qt ◽

Qt Syndrome

The review presents the recent data on genetic reasons of sudden cardiac death. Mutations discuss in gens associated with sudden cardiac death. Channalopathies, such as Brugada syndrome, long QT syndrome, short QT syndrome and catecholaminergic polymorphic ventricular tachycardia are characterized by arrhythmias in normal heart resulting from genetic anomalies in ion channels

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Mechanisms and clinical management of inherited channelopathies: Long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome

Heart Rhythm ◽

10.1016/j.hrthm.2009.02.009 ◽

2009 ◽

Vol 6 (8) ◽

pp. S51-S55 ◽

Cited By ~ 71

Author(s):

Elizabeth S. Kaufman

Keyword(s):

Ventricular Tachycardia ◽

Long Qt Syndrome ◽

Brugada Syndrome ◽

Clinical Management ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Short Qt Syndrome ◽

Long Qt ◽

Qt Syndrome

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Cardiac Channelopathies: Recognition, Treatment, Management

AACN Advanced Critical Care ◽

10.4037/aacnacc2018664 ◽

2018 ◽

Vol 29 (1) ◽

pp. 43-57

Author(s):

Kathleen T. Hickey ◽

Amir Elzomor

Keyword(s):

Cardiac Arrhythmias ◽

Arrhythmogenic Right Ventricular Dysplasia ◽

Interdisciplinary Teams ◽

Polymorphic Ventricular Tachycardia ◽

Molecular Testing ◽

Short Qt Syndrome ◽

Long Qt ◽

New Era ◽

Qt Syndrome ◽

Opening And Closing

The discovery of the human genome has ushered in a new era of molecular testing, advancing our knowledge and ability to identify cardiac channelopathies. Genetic variations can affect the opening and closing of the potassium, sodium, and calcium channels, resulting in arrhythmias and sudden death. Cardiac arrhythmias caused by disorders of ion channels are known as cardiac channelopathies. Nurses are important members of many interdisciplinary teams and must have a general understanding of the pathophysiology of the most commonly encountered cardiac channelopathies, electrocardiogram characteristics, approaches to treatment, and care for patients and their families. This article provides an overview of cardiac channelopathies that nurses might encounter in an array of clinical and research settings, focusing on the clinically relevant features of long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

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The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-020-02505-y ◽

2021 ◽

Author(s):

Shanna Hamilton ◽

Roland Veress ◽

Andriy Belevych ◽

Dmitry Terentyev

Keyword(s):

Cardiac Arrhythmia ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Polymorphic Ventricular Tachycardia ◽

Genetic Mutations ◽

Strong Basis ◽

Functional Changes ◽

Intracellular Ca ◽

Qt Syndrome

AbstractSudden cardiac death due to malignant ventricular arrhythmias remains the major cause of mortality in the postindustrial world. Defective intracellular Ca2+ homeostasis has been well established as a key contributing factor to the enhanced propensity for arrhythmia in acquired cardiac disease, such as heart failure or diabetic cardiomyopathy. More recent advances provide a strong basis to the emerging view that hereditary cardiac arrhythmia syndromes are accompanied by maladaptive remodeling of Ca2+ homeostasis which substantially increases arrhythmic risk. This brief review will focus on functional changes in elements of Ca2+ handling machinery in cardiomyocytes that occur secondary to genetic mutations associated with catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome.

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