The Impact of Genetic Testing on Clinical Management of Channelopathies
Advances in DNA sequencing technology and other types of genetic testing are having a greater impact on the management of cardiac channelopathies, such as long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. A clinical review published May 14 in the Journal of the American College of Cardiology examined the role of genetic testing in the management of these cardiac arrhythmic disorders of genetic origin.
Clinical responses to β-blockers among patients with LQTS are gene-specific in part, as is the response to the sodium channel blocker mexiletine. β-blockers are effective in patients with LQT1, LQT2 and LQT3 genetic subtypes of LQTS, but less effective in female LQT2 patients. Mexiletine has been shown to shorten the QT interval in LQT3 patients, but not in LQT1 or LQT2 patients. Mexiletine may be given as a potentially useful addition to β-blockers.
The triggers for arrhythmias also are gene-specific in LQTS patients. LQT1 patients are at particular risk of arrhythmias during physical exercise or emotional stress. These patients are advised to avoid physical or mental stress. LQT2 patients are extremely sensitive to sudden noises, especially when resting; they are advised to remove telephones and alarm clocks from their bedrooms.
Once a genetic mutation for LQTS has been identified in patients, their entire families should undergo genetic testing for that specific mutation to identify carriers of the mutation with normal QT findings on electrocardiograms. This so-called cascade screening can identify individuals with normal QT who might be at risk of potentially life-threatening arrhythmias.
"Cascade screening forcefully demonstrates that molecular biology and genetics can no longer be regarded as tools for researchers, but nowadays represent an essential component of good medical care," write the authors. Further, "it should be clear to everyone in cardiology and medicine that genetics and clinical management of [cardiac channelopathies] are tied together and that nowadays it is seldom possible to efficiently treat the affected patients without keeping into account what has been learnt from genetic testing," they add.
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