By Julie Rutberg, MS, CGC
Genetic Counsellor
And
Michael Gollob, MD, FRCPC
Director, Genetic Arrhythmias Research Laboratory
University of Ottawa Heart Institute
Updated December 2006
Genetic research in arrhythmias has made tremendous advances in recent years and we are starting to see genetic testing impact the clinical care and evaluation of patients with arrhythmias. Genes, the basic unit of heredity, are the DNA sequences that code for proteins. Alterations in some genes are quite common and lead to the diverse physical characteristics of individuals. When alterations occur in genes that make proteins that are important in regulating the heart rhythm, such alterations may predispose to the development of dangerous heart rhythms. These alterations are called mutations, and everyone has mutations and proteins that do not function properly. Genetic research aims to identify which gene or genes are altered, and how this may cause a condition. For example, research on Long QT syndrome in the 1990s led to the discovery of several genes that are crucial to normal heart rhythms. This research took many years and involved hundreds of families affected with Long QT syndrome.
The discovery of the Long QT genes in turn led to more research and discoveries of other genes involved with arrhythmias. There are genetic mutations known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy (ARVC) and some other types of cardiomyopathies. However, genetic testing does not detect a mutation in every person with these conditions. This could be for two reasons. First, it is likely that there are other genes, yet to be discovered, that cause these conditions. Secondly, there are likely some types of genetic alterations that are not detected with the current methods used in genetic testing. Thus, researchers continue to study individuals and families with inherited arrhythmia conditions, but in the meantime, some genetic testing is now available clinically.
When is genetic testing helpful?
Genetic research has led to clinical laboratories offering genetic tests and there are several situations where this is helpful for patients, for their family members and for the physicians. Genetic testing can be used in conjunction with standard cardiac testing such as ECGs and treadmill tests to determine if someone has an arrhythmia condition. There are two situations where genetic testing might be a useful addition. The first is if there is uncertainty about the exact diagnosis. For example, a patient could have a history of fainting spells, but does not quite meet the diagnostic criteria for Long QT syndrome (LQTS) based on the family history and cardiac tests. Genetic testing of 5 genes that are known to cause LQTS can be performed. If a gene alteration known to cause LQTS is found, that would make the diagnosis of LQTS syndrome in this patient much more likely. However, if no gene alterations are found, the genetic tests do not ‘rule out’ LQTS, since the tests do not find a mutation in 100% of people definitely affected with LQTS. In fact only 70% of people who are definitely affected by LQTS are found to have a gene alteration, using the current testing methods.
In cases of autopsy-negative sudden cardiac death, there is often uncertainty about the diagnosis. Genetic testing can be performed if DNA samples are saved from an autopsy, even if the samples are many years old. Determining the exact diagnosis in a case of sudden cardiac death can be helpful in providing an answer for why the death occurred, providing closure to the family and community. In addition, the diagnosis can help determine the risk of.