Impact of Genetics on the Clinical Management of Channelopathies
The following are 10 points to remember from this state-of-the-art review dealing with genetic testing in patients with long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS):
1. In patients with LQTS, a responsible mutation can be identified in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3) in 75% of patients and in 1 of 13 other genes in 5% of patients.
2. In patients with LQTS, genetic testing plays a minor role for risk stratification and predicting the response to drug therapy.
3. Genotyping allows patient-specific counseling, such as avoidance of swimming in LQT1 and avoidance alarm clocks in LQT2.
4. A major role of genetic testing is to identify genotype-positive family members of a proband with LQTS who are phenotype-negative; such individuals should be counseled on avoidance of QT-prolonging drugs.
5. Approximately 50% of cases of CPVT are caused by a mutation in RYR2, which codes for the ryanodine receptor/calcium release channel; rare causes of CPVT are a mutation in CASQ2, which codes for calsquestrin 2, and a mutation in TRDN, which codes for triadin.
6. Genetic testing for CPVT is recommended for patients suspected to have CPVT based on clinical findings.
7. Mutation-specific testing should be performed in family members of genotype-positive probands with CPVT to identify at-risk relatives.
8. The yield of genetic testing is 25% in patients with BrS; mutations in SCN5A, which codes for the α-subunit of the sodium channel, are most commonly responsible for BrS.
9. Genetic testing for BrS can be helpful when the clinical picture is unclear.
10. Mutation-specific genetic screening is recommended for family members of a proband with a positive BrS genotype.
Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Heart Failure and Cardiomyopathies, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Lipid Metabolism
Keywords: Brugada Syndrome, KCNQ1 Potassium Channel, Baroreflex, Long QT Syndrome, Genetic Testing, Sodium Channels, Calcium, Mutation, Ryanodine Receptor Calcium Release Channel, Muscle Proteins, Tachycardia, Ventricular, Phenotype, Carrier Proteins, Genotype, Channelopathies
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