Cardiovascular Genetics

Why is it important to consider genetic testing for a heart condition? 

Genetic testing may provide more information on your or a loved one’s heart condition, and may confirm or establish a diagnosis. The results of testing may also provide useful information with regards to treatment and risk reducing strategies to manage heart health for those affected. 

Since hereditary heart diseases have the potential to affect one or more family members, understanding which change in which gene is responsible can also be helpful in guiding testing options for other family members and identifying which family members need more or different medical care than might otherwise be expected, and which family members may be lower risk than expected based on family history alone. 

How do I know if I should get genetic testing?

If you think your family may have an inherited heart condition, it is important to collect information about your family medical history. Consider which family members may have had heart conditions, died suddenly or unexpectedly, or had any other major medical problems. 

Specifically, it is helpful to gather information related to whether or not you or any of your family members have ever experienced any of the following:

Heart conditions present at birth

Irregular heartbeat (arrhythmia)

Sudden and unexplained cardiac arrest

Unexplained fainting during exercise or emotional stress

Unexplained seizures 

Heart failure under 60 years of age

ICD/Pacemaker installed under 50 years of age

Early heart attack, coronary heart disease, or stroke (men under 55, women under 60)

Untreated high cholesterol levels

Enlarged heart

Enlarged aorta or aortic aneurysm at less than 55 years of age 

An individual or family member who is the most seriously affected is typically the ideal candidate for testing. This is the individual in the family for whom there is usually the highest likelihood of identifying a related genetic change—and understanding what it means. In many cases, however, this just isn’t possible or the ideal family member for testing has already passed away. Genetic testing can still be valuable for other family members in these situations too.

Common Hereditary Heart Diseases

There are many different kinds of hereditary heart diseases. Some affect the heart’s structural integrity (ex. Hypertrophic Cardiomyopathy), others affect the heart’s rhythm (ex. Long QT syndrome), and some don’t even affect the heart directly, but instead affect an individuals’ heart health through cholesterol levels (ex. Familial Hypercholesterolemia). 

Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH) is an inherited condition that affects an individual’s ability to process low-density lipoprotein (LDL) or “bad” cholesterol. When untreated, FH can cause dangerously high levels of LDL. When LDL levels in the blood are high, they can be deposited along the walls of veins and arteries, leading to athlerosclerotic plaques. These can harden veins and arteries, constricting and impeding blood flow which can increase an individual’s risk for serious heart conditions such as coronary artery disease, heart attack, or stroke.

Heart attacks and strokes are common in the general population, particularly at older ages and specifically for individuals who have other risk factors for cardiovascular disease. Many Americans have high cholesterol and for most of these individuals, FH is not the underlying reason for the high cholesterol. For individuals with FH, however, heart attacks or strokes may occur at young ages and cholesterol may be high even when an individual does not have other risk factors. 2011 guidelines from the National Lipid Association indicate that FH should be suspected when LDL is >190 or non-HDL cholesterol is >220. 

There are three genes associated with FH (APOB, LDLR, and PCSK9), and when one of these genes carries a mutation, an individual can have high LDL levels starting as early as at birth. Because FH is an inherited disorder, if one person if diagnosed with FH, it is incredibly important to inform family members to discuss further screening.

FH is typically inherited in an autosomal dominant pattern. So, if one parent has FH and carries one of the mutated genes, there is a 50% chance that their child will inherit the gene associated with FH, and a 50% chance that their child will be an unaffected non-carrier. 

FH is fairly common from a genetics perspective, occurring in 1 in every 250 people. Unfortunately, it is estimated that 9 out of every 10 individuals with FH do not know that they have FH. An early diagnosis with FH is important because there are effective treatments available to manage FH that can significantly reduce an individual’s cardiovascular risks. 

Some individuals do carry two mutations related to FH (“Homozygous FH”). This causes more extreme levels of high cholesterol with cardiovascular risks (ex. stroke, heart attack), often manifesting at younger ages than in individuals with only one mutation related to FH.

Hypertrophic Cardiomyopathy

Familial Hypertrophic Cardiomyopathy (HCM) is a heart condition that is characterized by the thickening of the muscles that make up the heart. This can keep the part from beating properly or can impede the flow of oxygen-rich blood to the rest of the body. Individuals with HCM are at an increased risk for a number of complications such as irregular heartbeats (atrial fibrillation), sudden cardiac arrest, or heart failure.  

There are numerous genes associated with HCM; the most common are MYH7, MYBPC3, TNNT2, and TNNI3; mutations in other genes can be less common causes of HCM, and other possible associated genes are still being studied and discovered. 

Since HCM  is inherited in an autosomal dominant pattern, if one parent has HCM, there is a 50% chance that their child will inherit the gene with the mutation associated with HCM, and a 50% chance that their child will be an unaffected non-carrier. 

HCM is one of the most common genetic heart diseases, affecting 1 in every 500 people. Diagnosing HCM as soon as possible is important in order to receive treatment and prevent serious complications, including sudden death. 

Long QT Syndrome

Long QT Syndrome is a genetic heart condition that affects the heart’s electrical conduction system, which influences the heart’s beat, or rhythm. This heart condition can cause the heart to have fast and chaotic heartbeats, which can lead to fainting spells or even seizures. These cardiac events can be triggered by certain medications, loud noises, emotional distress, or exercise. The specific triggers may depend on the subtype of LQT. In some cases, the heart will beat so erratically for a long period of time that it can lead to sudden death. If an individual is aware that they have LQT, however, there are ways to manage the condition. For example, people with LQT should avoid certain medications.  

There are several genes that are associated with Long QT, and carrying a single mutation in any one of those genes may cause Long QT. 

Because this condition is inherited in an autosomal dominant pattern, if one parent has Long QT, there is a 50% chance that their child will inherit the gene associated with Long QT, and a 50% chance that their child will be an unaffected non-carrier. 

Although the exact frequency of Long QT is not known, it is estimated to occur in 1 in every 2,000 people. Early diagnosis of Long QT is important in order to receive treatment and proper surveillance and management of environmental triggers.

Interested in learning more about LQT or other hereditary cardiovascular conditions associated with sudden death? Check out our Patient Stories podcast interview with genetic counselor Nori Williams. 

How Can Genetic Counseling Help?

We understand how disorienting it can be to try to figure out what kind of genetic testing might help you, or to get a genetic test back and not know what to do with the information! If you think that you may be at risk for a hereditary cardiovascular genetic condition, we highly recommend that you speak with a genetic counselor before having any testing done, if possible. Working with a genetic counselor can ensure that you have a good understanding of your options and can also help with cost savings since a genetic counselor can help guide you toward the best, high quality test that makes the most sense for you, often avoiding the need to do additional testing at additional cost down the road.

A cardiovascular genetics consult includes review of your family health history, with a focus on known cardiovascular diagnoses as well as signs and symptoms that may be associated with hereditary cardiovascular conditions. Your genetic counselor will discuss with you not only the possibility of a hereditary cardiovascular condition that could be diagnosed with the aid of genetic testing, but also how a clinical diagnosis (ex. work-up by a knowledgeable cardiologist or electrophysiologist) may be an important part of interpreting certain genetic test results. Your genetic counselor will also discuss how your test results might impact other family members. In some cases, your genetic counselor may suggest initiating testing with a different family member, when feasible, as this sometimes makes more targeted and informative testing possible for you and potentially for other family members. You can book a cardiovascular consult with a genetic counselor here.