Welcome to Metis Genetics’ blog, Metis on the Move, and our three-article series on genetic testing for cardiogenetic conditions.
Over the next several weeks, we will explore:
the benefits of genetic testing in this specialized area of medicine;
common inherited cardiac conditions and how to identify patients who would benefit from testing; and
where to refer patients for genetic testing, as well as types of possible test results.
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Part 1- Hold it Close to Your Heart: The Potentially Life-saving Benefits of Genetic Testing for Specific Cardiac Conditions
The fields of genetics and genetic testing, and the technologies used to uncover variants in our DNA, have expanded and improved in leaps and bounds over the last decade. Genetic testing for specific changes that can affect patients’ health has been used routinely in several areas of medicine, including the prenatal, reproductive, pediatric and cancer fields. The field of cardiac genetics, or cardiogenetics, although a bit newer than some of the others, has followed suit.
Heart disease is the number one cause of death worldwide 1, and tends to run in families. Common or multifactorial conditions, such as hardening of the arteries, are generally due to a variety of factors, including environmental factors such as diet, physical inactivity and tobacco use. Predictive genetic testing for risk in the context of these common types of conditions is an emerging area, but currently is usually not clinically useful, as there is generally such a large environmental effect. Genetic testing does becomes useful for certain cardiac conditions with a strong genetic effect. These particular conditions are generally caused by changes in a single gene. When there is an individual who has a clinical diagnosis, or a potential clinical diagnosis, of inherited heart disease, particularly if they have a positive family history, genetic testing can be valuable. To maximize the chance of detecting a potential causative mutation, initial genetic testing ideally should be offered to a member of the family who has:
- Definite clinical disease
The most severe manifestations
The youngest age at diagnosis2
Genetic testing for certain cardiogenetic conditions can provide many important benefits. The first is to help clinicians come to an accurate diagnosis. Genetic test results should not be used as a substitute for careful clinical evaluation of family members, which remains the primary basis for diagnosis of inherited heart disease. However, genetic testing is a part of the diagnostic criteria for several cardiogenetic conditions, such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and long QT syndrome (LQTS). Having an accurate diagnosis is the first step in the proper care of the patient.
The next benefit of genetic testing is the appropriate management of the patient based on their diagnosis and test results. The use or the avoidance of certain medications, cardiac interventions such as implanting a defibrillator, exercise reduction, and the avoidance of alcohol are all examples of management changes that can be made based upon test results. Healthy behaviors, including the avoidance of recreational drugs, are particularly important for individuals with genetic variants predisposing them to cardiac conditions. For some conditions, test results can change the management of patients who already have a clinical diagnosis. This is the case with LMNA-related dilated cardiomyopathy, which is caused by pathogenic variants in the LMNA gene.3
A third benefit of genetic testing for cardiogenetic conditions is the screening of family members. Many cardiogenetic conditions are autosomal dominant, which means that a single abnormal gene on one of the first 22 non-sex (autosomal) chromosomes from either parent can cause the condition, and that all first degree relatives of the identified patient are at 50% risk for having the same mutation and the resulting condition.4 Clinicians use what is called cascade screening to identify at-risk individuals in a family once a pathogenic variant (mutation) has been identified in the first tested affected individual, or the index case. Once this mutation associated with the condition has been identified in the index case, genetic testing is then extended to all of the individual’s at-risk relatives. This process is repeated as more affected individuals or pathogenic variant carriers are identified. Cascade genetic screening is key because it can identify asymptomatic affected family members and pre-symptomatic carriers of pathogenic variants.5 This process can save lives by helping to prevent sudden deaths in the family that might have been caused by an undiagnosed heart condition. In addition, early diagnosis and prompt treatment can help prevent severe disease or complications that can occur with late diagnosis.
A final important potential benefit of genetic testing for cardiogenetic conditions is the ability to utilize prenatal planning. Once a pathogenic variant has been identified in a family, the combined use of in-vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD) is an option. These procedures allow embryos from a successful IVF cycle to be screened for the known familial pathogenic variant. Individuals and families can choose to only implant embryos without the variant, thus greatly reducing the chance of passing the variant screened for on to the next generation. This is an ethically complex area of genetics as many cardiogenetic conditions are adult-onset conditions associated with a high quality of life. Genetic counseling of individuals and families interested in pursuing these reproductive technologies is highly recommended.
There are many key advantages to genetic testing for cardiogenetic conditions, including potentially saving the lives of asymptomatic patients. In our next article in this series on cardiogenetics, we will discuss the wide range of inherited heart conditions, and how to identify patients that may benefit from genetic testing.
Please visit the following resources for more information
Genetic testing registry: https://www.ncbi.nlm.nih.gov/gtr/
The National Society of Genetic Counselors: www.nsgc.org
Genetic Alliance: http://www.geneticalliance.org
Genetics Home Reference: http://ghr.nlm.nih.gov/
2. Genetic Evaluation of Cardiomyopathy - A Heart Failure Society of America Practice Guideline. Hershberger RE et al. J Card Fail. 2018 May; 24(5):281-302.
5. Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Hershberger RE et al.; ACMG Professional Practice and Guidelines Committee. Genet Med. 2018 Jun 14.
Kristina Habermann, MS, CGC, MBA
Kristina is a board-certified genetic counselor and a long-time enthusiast of the use of genetics to improve patients’ health and lives. She has practiced as a genetic counselor and worked in Sales and Marketing educating clinicians and patients about the risks and benefits of genetic testing; ranging from prenatal to cancer to pharmacogenetic testing in psychiatry. She particularly enjoys writing about genetics and genetic counseling and is currently the Assistant Program Director of the Genetic Counseling Graduate Program at LIU Post.