What is Feline Hypertrophic Cardiomyopathy? 

Hypertrophic Cardiomyopathy (HCM) is a disorder in which the heart muscle wall increases in thickness, decreasing the volume of blood the heart can hold and the efficiency of the heart muscle to pump blood, eventually leading to heart failure. It is the most common cardiac disease in cats. 

Hypertrophic Cardiomyopathy (Discovered in the Maine Coon) is one of two variants included in Wisdom Panel feline breeder testing, along with Hypertrophic Cardiomyopathy (Discovered in the Ragdoll). Although the names indicate an association with certain breeds, we know that both variants can occur in other breeds, they were simply first discovered in that breed. For more information about the frequency with which these variants are found by breed, please see here. 

The study: 

In 2024, a global HCM working group of feline scientists and geneticists, including a Wisdom scientist, published a study aligning the current understanding of the disease-causing potential (pathogenicity) of feline hypertrophic cardiomyopathy variants using human genetic classification guidelines. Five breeds were included in the study: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair, along with six feline HCM variants.  

It is appropriate that this group of scientists should use human guidelines, as feline and human HCM have many similarities. HCM in humans was first identified as a genetically dominant disorder in 1960, with more than 1700 variants now known to be associated with the disease. What the researchers found was that some of the variants, which are occasionally available in commercial tests, have not been independently verified to cause disease. To rectify this problem, they used the American College of Medical Genetics (ACMG) guidelines, which classifies genetic variants using a category system based on a number of factors, including review of previous research, clinical studies and computer models, and pedigree analysis. The categories of variants based on the results of these factors are as follows: 

Only when there is enough evidence to indicate ‘likely pathogenic’ or ‘pathogenic’ can a variant be recommended for decision-making, for instance, genetic testing. 

What the researchers found is that although the mode of inheritance for the HCM Maine Coon (HCM-MCO) variant is not simple, it is closest to an autosomal recessive mode of inheritance, not dominant as previously reported. They found in the studied cats that there was a 13- fold increase risk for cats with 2 copies of the HCM-MCO variant. The HCM Ragdoll (HCM-RAG) variant was associated with disease, but the study lacked adequate statistical power to assign a definite risk score for the variant in that breed. One variant was not found in any of the studied cats. In contrast, none of the variants were found to cause statistically significant disease in the Sphynx, Devon Rex and British shorthair/longhair. Conclusions from the study: 

“Two variants were found to be pathogenic, and one variant was classified as likely pathogenic. However, practically we recommend limiting routine genetic testing to two variants in two breeds, i.e., the MYBPC3:c.91G > C [A31P] in Maine Coon and the MYBPC3:c.2453C > T [R818W] variant in Ragdolls. While their (homozygous) presence increases the risk of developing HCM in those two breeds, they are virtually absent in other major breeds: the recommendation to specifically screen for these variants in the breeds in which they were originally described, but not other breeds, thus remains.” 

 

However, the group pointed out that the study lacked testing for domestic random-bred or household cats or other breeds, and the study utilized panel-testing results of several thousand cats from Wisdom breeders, so there is benefit to broad screening of breeds for disorders, as long as reporting of significance in breeds is appropriate. One variant, MYH7:c.5647G > A [E1883K], was not found in any of the studied cats of all five breeds, but using the ACMG classification, three pathogenic criteria were fulfilled, resulting in classification as “likely pathogenic.”