Family Ties: Exploring the Role of Genetics in Hypertrophic Cardiomyopathy (HCM)
Genes can play a big role in both your overall health and your risk of inheriting certain diseases. As the scientific community has learned more about the role of genetics in diseases over the past two decades, knowing your family medical history is becoming increasingly important. Case in point— a heart condition called hypertrophic cardiomyopathy (more frequently referred to as HCM). HCM is estimated to affect approximately between 1 in every 500 people and 1 in 200 people and is also the most common genetic heart condition—despite this, many people with the disease don’t even know they have it.*[1],[2],[3]
What is HCM?
In someone with HCM, the walls of the heart become thicker than they should be, making it difficult for the heart to efficiently pump oxygenated blood throughout the body.[4] This means that a heart affected by HCM has to work harder, so those with HCM can experience a lack of energy, a rapid heartbeat, chest pain, shortness of breath or other symptoms, especially in the context of physical activity.[5]
Recognizing the symptoms of HCM is important in getting an early and accurate diagnosis. Historically, HCM has been hard to diagnose since patients can have mild, nonspecific symptoms, symptoms that mimic other conditions, and in some case, no symptoms at all.[6] Possible symptoms that signal HCM can include shortness of breath, dizziness, fainting, or heart palpitations. These are also common symptoms of asthma, high blood pressure, and more. Only a healthcare provider can determine whether your symptoms may indicate HCM.
HCM: The Most Common Genetic Heart Condition
It’s estimated that approximately 30-60% of all cases of HCM are genetic, meaning that they are caused by a mutation in a gene that causes encoded protein not to work properly.[7] Every person inherits two sets of chromosomes—one from their mother and one from their father—that are each made up of specific genes. While there are a number of different ways in which diseases can be passed down through families, in the case of HCM, sometimes a person only needs to inherit a single copy of the mutated gene to cause the disorder. A person who has one of the genetic mutations that causes HCM has a 50% chance of passing it onto their children.
Jil C. Tardiff, M.D., Ph.D., a professor of biomedical engineering, medicine, and cellular and molecular medicine at the University of Arizona College of Medicine and a paid spokesperson for Bristol Myers Squibb, has been studying the genetic causes of HCM for years. “I was intrigued by the fact that HCM patients have such a wide array of symptoms. I really wanted to delve into the genetic causes of this condition in its earliest stages and how this has potential to impact the progression of the disease,” says Dr. Tardiff.
Unlocking the Science Behind HCM
To get to the root of the disease, you need to look at the science behind the genetic mutations that can cause this disease—a body of knowledge that Dr. Tardiff says is continuing to grow and evolve.
“The majority of genetic cases of HCM are caused by mutations in the genes that make up the sarcomere,” explains Dr. Tardiff.[8] The cardiac sarcomere is a protein complex in the heart that controls the contraction and relaxation of cardiac muscle. To date, multiple genetic mutations associated with HCM have been identified in at least 11 sarcomere genes.[9] Dr. Tardiff says that the total number of genetic mutations that can lead to HCM is an ongoing discussion among the leading experts in the field. Overall, experts agree that more data needs to be collected and research done in order to identify other potential mutations and causes.
Are All Cases of HCM Inherited?
While there is an established genetic link for many people diagnosed with HCM, it is important to note that this is not always the case. Non-inherited cases of HCM are defined as those where there is no indication of anyone else in the family with HCM (past or present) or when genetic testing does not identify any of the most common genetic mutations associated with the disease.[10]
The Growing Role of Genetic Testing
When a patient is diagnosed with HCM, their doctor may suggest genetic testing. In fact, recent updates to the American Heart Association and the American College of Cardiology guidelines highlight the increasing importance of genetic testing in the diagnosis and management of HCM. A discussion about the role of genetic testing, which can involve collecting a DNA sample by swabbing the inside of your cheek, is now a standard part of the conversation between HCM patients and their physicians.[11]
In addition, “pre- and post-testing genetic counseling is recommended for individuals undergoing genetic testing,” Dr. Tardiff says. Pre-testing genetic counseling is important to ensure patients understand the pros and cons of testing and post-testing genetic counseling can help patients interpret and understand the implications of their results. If genetic testing does reveal a known genetic mutation associated with HCM, patients should consider informing their close family members.
If your genetic test is positive for an HCM gene, ask your doctor who it is appropriate to share that information with.
Visit CouldItBeHCM.com to learn more.
Sources:
* CARDIA study (published in 1995) is a multicenter, US-population-based echocardiography study of 4,111 subjects (aged 23-35), identified the prevalence of HCM as 1:500 people in the general population. The 2015 Semsarian publication identified that the prevalence of HCM-gene carriers could be as high as 1:200.
[1] Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation. 1995;92(4):785-789.
[2] Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254.
[3] American Heart Association. Hypertrophic cardiomyopathy (HCM). Updated November 17, 2020. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/hypertrophic-cardiomyopathy.
[4] American Heart Association. Hypertrophic cardiomyopathy (HCM). Updated November 17, 2020. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/hypertrophic-cardiomyopathy.
[5] American Heart Association. Hypertrophic cardiomyopathy (HCM). Updated November 17, 2020. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/hypertrophic-cardiomyopathy.
[6] University of Maryland Medical Center. Hypertrophic cardiomyopathy types, symptoms and causes. Accessed May 24, 2022. https://www.umms.org/ummc/health-services/heart-vascular/services/hypertrophic-cardiomyopathy/types-symptoms-causes.
[7] Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e558-e631.
[8] Velicky L, Jakovljevic DG, Preveden A, Golubovic M, Bjelobrk M, Ilic A, Stojsic S, Barlocco F, Tafelmeier M, Okwose N, Tesic M, Brennan P, Popovic D, Ristic A, MacGowan GA, Filipovic N, Maier LS, Olivotto I. Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy. BMS Cardiovascular Disorders. 2020; 516.
[9] Maron BJ, Maron MS, Semsarian C. Genetics of Hypertrophic Cardiomyopathy After 20 Years: Clinical Perspectives. Journal of the American College of Cardiology. 2012; 60(8)705-715.
[10] Ommen ST, Mital S, Burke MA, Day SM, Deswal A, Elliot P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P, 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Circulation. 2020; 142:e558-e631.
[11] Ingles J, Burns C, Bagnall RD, Lam L, Yeates L. Sarina T, Puranik R, Briffa T, Atherton JJ, Driscoll T, Semsarian C. Nonfamilial Hypertrophic Cardiomyopathy. Circulation. 2017;10:e011620
