Jackie Tahiliani

Hypertrophic cardiomyopathy: a path down the yellow brick road

Jackie Tahiliani, M.S., CGC, Invitae Genetic Counselor

Hypertrophic cardiomyopathy (HCM), a complex disease that affects the heart muscle, initially captured the attention of physicians in the late 1950s as a “new” type of structural heart disease. Over the intervening decades, clinical advancements in cardiac imaging made the criteria for diagnosis of HCM clearer. Meanwhile, advancements in genomics led to the exponential decline in the cost of DNA sequencing, which opened the door to pinpointing the cause of common genetically heterogeneous conditions such as HCM.

For more than 20 years, genetic research into the cause of HCM has led to breakthroughs that enable genetic testing to play a larger role in early diagnosis and management of affected patients.1 Most recently, HCM-focused clinical and research trials have sought to incorporate a personalized-medicine approach to treating and managing HCM by combining clinical and genomic information. Much like Dorothy’s yellow brick road, the research path for HCM has led to discovery and enlightenment, especially with the increased incorporation of genetics into the field of cardiology.

HCM is characterized by a thickening of the heart muscle, which occurs most commonly the left ventricle. This structural change to the muscle causes the affected area to pump harder to sustain normal blood flow output and increases strain on the heart muscle. The most common forms of HCM are caused by genetic changes that alter the structure or function of sarcomeres, which are proteins involved in muscle contraction. Over a thousand distinct pathogenic variants have been reported in the sarcomere genes causing HCM.2 Pathogenic variants in these genes are identified in up to 40 percent of individuals with HCM who have no known family history, and in up to 60 percent of individuals with a family history of HCM.

Through genetic testing, Invitae is actively working to assist physicians in detecting the genetic cause for HCM. Our 16-gene HCM panel aids in identifying the pathogenic variant causing HCM in an affected individual—knowledge that can also be used to identify at-risk family members via follow-up family variant studies. The onset of disease with inherited forms of HCM is variable, even within families, as it can present anytime from infancy through adulthood. This makes genetic testing for a familial variant—or, in some cases, variants—an effective tool for family screening and subsequent early diagnosis and management.

HCM is reported to affect one in 500 people around the world, men and women equally. A recent study suggests that the prevalence may actually be higher because pathogenic variants in sarcomere genes are more common than previously thought; HCM is a familial disease; and asymptomatic carriers of pathogenic variants were not accounted for in initial prevalence calculations.3

Invitae’s mission is to bring affordable, accessible genetic testing services to all so that every affected individual has an opportunity to uncover a genetic diagnosis. With common diseases such as HCM, Invitae has the ability to directly impact a large, diverse group of patients and families coping with this disease.

More information about HCM is available in the webinar Diagnosis and management of hypertrophic cardiomyopathy, presented by Dr. Christopher Semsarian. An internationally renowned cardiologist and scientist, Dr. Semsarian studies the genetic causes of heart disease as well as how best to manage the health of individuals and families with inherited cardiac disorders.

Additional information and resources about HCM are available at:

1 Maron, BJ et al., J Am Coll Cardiol. 2012; 60:705-15.
2 Seidman, CE et al., Circ Res. 2011; 108:743-50.
3 Semsarian, C et al., J Am Coll Cardiol. 2015; 65:1249-1254.


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