A recent study of identical twins with HCM found significant variation in the expression of hypertrophic cardiomyopathy, even between twins carrying the same HCM-causing genetic mutation.
This paper concludes that epigenetics (things which influence expression of DNA like behavioral and environmental factors) greatly influence the expression of HCM genetic mutations.
The researchers studied 11 pairs of twins with HCM. 9 of the twin pairs had known HCM sarcomere mutations while 2 of the pairs had HCM of unknown cause. The siblings were followed for a time frame of between 5 to 14 years.
Researchers compared left ventricular wall thickness, left atrial size and left ventricular ejection fraction. Differences were found in the left ventricular wall thickness of all 11 pairs of twins, while left atrial size was similar in 3 of the 9 twin pairs who carried HCM mutations. Left ventricular ejection fraction was different in 4 of 7 twin pairs.
The researchers theorize that similarities in left atrial size may be due to impaired ventricular relaxation directly tied to sarcomere dysfunction. In contrast, environmental factors yield more influence over ventricular function.
HCM epigenetics is a field ripe for research. As HCM patients, we hope that it will yield actionable data in the near future.
A recent discovery by British researchers sheds light on how a type of common genetic mutation – a so called “common variant” – influences the expression of hypertrophic cardiomyopathy caused by mutation(s) in the cardiac sarcomere.
How do Common Variants Impact Sarcomere Mutations?
This research, funded by the British Heart Foundation and spearheaded by Dr. Hugh Watkins of the University of Oxford, explains why some individuals with a particular sarcomere mutation develop a severe case of HCM, while their family members with the same mutation may develop only mild HCM symptoms or show no signs of the disease at all. It also may explain why people who lack sarcomere mutations develop the disease.
The researchers compared the DNA of 2,780 people with HCM and 47,486 people without HCM and found that common variants acting in concert with rare sarcomere mutations determine whether a person will develop HCM.
Common Variant HCM Not Hereditable
In addition, the researchers found that HCM attributable to common variants alone is unlikely to be passed on to future generations. This is good news for the children of HCM patients caused by common variants.
Watch your Blood Pressure
Lastly, this paper found that high diastolic blood pressure was associated with the development of HCM caused by common variants. Hence, keeping blood pressure under control is something that patients can do to minimize their risk of developing HCM in the future.
The highly anticipated 2020 American Heart Association/American College of Cardiology Guidelines for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy have been released.
This document, drafted with reference to published HCM literature, and with input from a committee of HCM experts with broad expertise, updates the prior version published in 2011. It contains clinical practice guidelines for the broad spectrum of issues which may confront medical professionals as they approach the diagnosis and treatment of patients and families affected by hypertrophic cardiomyopathy.
Continue reading “2020 AHA/ACC HCM Diagnosis & Treatment Guidelines Released”
This story in the Wall Street Journal about genetic testing shows the speed of changes in the medical community’s understanding of how and whether certain genes cause hereditary disease.
The article quoted Dr. Jodie Ingles, a geneticist from the University of Sydney in Australia who specializes in HCM and has published a recent article on the subject. Dr. Ingles said that 22 out of 33 genes comprising a genetic testing panel commonly used to test for HCM had either limited or no evidence of being disease causative.
Continue reading “Wall Street Journal Highlights Risks in Genetic Testing”
A recent study published in Circulation suggests that clinical testing of kids who are first degree family members of HCM patients (i.e. siblings and children of those who have already been diagnosed with HCM) could be improved by starting testing at a younger age. And, genetic testing should further improve diagnosis and treatment for this group.
Continue reading “When Do You Screen Your Kids For HCM?”
MyoKardia is collaborating with 23andMe, a genetic testing company which provides ancestry and health information directly to consumers, to create an online patient community intended to advance research efforts related to hypertrophic cardiomyopathy. The companies plan to allow 23andMe customers access to the latest information about HCM, as well as the opportunity to participate in research.
The companies will use a custom designed survey to collect baseline and follow-up data from HCM patients. They are hopeful that this collaboration will yield unique insights into HCM.
Research findings gained through the collaboration will be shared with HCM patients through the 23andMe platform. Currently more than 6,000 HCM patients are customers of 23andMe
More details of the collaboration can be found:
Press release from MyoKardia and 23andMe
DISCLOSURES: HCMBeat has received unrestricted educational grants from MyoKardia. Additionally, Cynthia Burstein Waldman of HCMBeat serves as a Patient Advisor on the Steering Committee for MyoKardia’s Explorer trial.
According to this study published recently in the Journal of the American College of Cardiology, whole genome testing may sometimes be used to identify the gene(s) responsible for HCM when targeted genetic testing (the type used in the clinical setting) has been inconclusive.
In particular, the study found the responsible gene(s) in 9 of 26 families (20%) in whom targeted testing had previously been inconclusive.
When used as the initial form of genetic testing, whole genome sequencing identified the responsible HCM gene in 5 of 12 families, or 42%.
According to this article in Wired U.K., a whole genome sequencing test costs about $600 and takes just a few weeks to complete. On the other had, the cost of data storage necessary to store such a large amount of collective data is, according to this article, prohibitively high.
If not for everyone, perhaps whole genome sequencing could be used in families where traditional genetic testing has proven inconclusive. Time will tell.
This recent article published in Nature discusses several real-life scenarios in which patients were mistakenly diagnosed with serious genetic cardiac conditions, including HCM, as a result of erroneous direct-to-consumer genetic testing.
These misdiagnoses directly resulted from misinterpretation of raw data by third party interpretation services that were working with raw data provided to them by direct-to-consumer genetic testing companies.
After medical testing, none of the patients discussed in the highlighted cases were ultimately found to have disease or be in need of medical intervention, though all underwent unnecessary medical testing and/or invasive procedures. Some even made radical lifestyle changes as a result of the erroneous genetic information.
This article demonstrates the unreliability of direct-to-consumer genetic testing, which has the potential to cause great upheaval to both patients and the medical system.
As always, patients seeking genetic testing should do their homework. Genetic testing for heart conditions is best when done by the experts – cardiac genetic counselors!
A recent editorial published in Circulation: Genomic and Precision Medicine suggests that current HCM screening protocols may need adjustment to account for recent findings by a study by researchers in the Netherlands. The Dutch study, published in the same journal, found that of 620 relatives of HCM patients who underwent genetic testing, 43% were found to be genetically positive for HCM, while 30% were diagnosed with HCM at the initial screening. 16% more went on to develop HCM during 7 years of repeated cardiac evaluation.
On the other hand, the 57% of relatives found to be genotype-negative were released from clinical HCM follow-up.
The Australian authors of the editorial, Semsarian and Ingles, note that current screening protocols would have failed to identify the 6 children (15%) who were diagnosed under the age of 12, half of which had a particularly malignant family history.
Additionally, few teens were diagnosed with HCM, which stands in contrast to current opinion that HCM is most likely to develop during adolescence. Indeed, most newly diagnosed family members were older than the age of 36, with 44% being over the age of 50.
Lastly, Semsarian and Ingles note their concern with general utilization of the Dutch practice of releasing a gene negative family member from serial follow up since the impact of all genes which have a role in causing HCM is not yet known while new genes which may cause HCM are still being identified.
Semsarian and Ingles also note that the Dutch patient sample differs from more typical patient populations found in the U.S. and Australia where causes of HCM are more diverse and cannot be easily tied to a specific gene.