A Winn Foundation Report On ...

Hypertrophic Cardiomyopathy in Maine Coon Cats

by Susan Little, DVM, Diplomate ABVP (Feline)

The two primary researchers into heritable hypertrophic cardiomyopathy (HCM) in Maine Coon cats are Dr. Mark Kittleson of the University of California at Davis and Dr. Kathryn Meurs of The Ohio State University. Both researchers were present at the Feline Genetic Disease Conference for presentations on HCM and question and answer sessions with both veterinarians and breeders.

Dr. Kittleson's presentation began with an overview of HCM in humans, where it is known to be inherited in an autosomal dominant fashion and has an adult onset. While there are currently over 100 mutations identified in seven different genes that can be responsible for HCM in people, the clinical signs and progress of the disease are often the same. The most common genetic defect involves a mutation in a gene that codes for the structure of an integral muscle protein (the beta-myosin heavy chain) in the individual heart muscle cell. Myosin is a protein that makes up about 65% of all the protein in a muscle cell. It consists of long chains of polypeptide components that are joined to each other by side chains. Myosin is one of the proteins responsible for contraction of heart muscle.

In cats, HCM is the most common cardiac disease. Most cats are middle-aged at the onset of their clinical symptoms, but patients as young as one year old and as old as 13 years have been identified. The average cat with severe HCM and heart failure lives for only several months despite therapy.

The first investigations into HCM in Maine Coons started when Marcia Munro, a private cat owner from Connecticut, contacted Dr. Kittleson about her affected Maine Coon cat and the related cats she had identified with HCM. All the cats from the cattery of origin were ultrasounded, and one unaffected male was bred to three affected females to start a research colony. In the research colony, ultrasounds were done starting at three to six months of age and were done every four to eight months afterward. Breeding records showed that HCM was inherited as an autosomal dominant trait in this colony. Breeding an affected cat to any other cat always produced at least one affected kitten in the litter. Equal numbers of males and females are affected. In Dr. Kittleson's colony, no cats with HCM were identified before one year of age when test breedings were done between affected cats and non-affected cats. The disease was often evident by two years of age and could be very severe by two to four years of age. Males seemed to have more severe disease and were affected earlier. When affected cats were bred to other affected cats, however, HCM appeared as early as three months of age; severe disease could occur by six to 18 months of age and males and females were affected in the same way. In the general cat population, cats with severe HCM will usually die of their disease. More males die of HCM and there may be no symptoms until the sudden death of the cat.

Dr. Kittleson identified certain characteristics of the HCM in Maine Coon cats that can be seen on ultrasound. Two changes in particular, called systolic interior motion of the mitral valve and papillary muscle hypertrophy, are commonly seen in Maine Coons with HCM. Dr. Meurs investigated the possibility that the genetic defect in HCM in cats is similar to that in people (i.e., it is in the beta-myosin heavy chain). Her studies found, however, that while cats often had genetic differences in the beta-myosin heavy chain, they were not differences that affected the production of the protein. Attention has now turned to other genes that make proteins that are part of the contractile element (the assembled proteins responsible for contraction) in heart muscle to determine if one of them is responsible for familial feline HCM. These include the myosin light chains and myosin binding protein C genes. In humans there is a rare form of HCM that involves a defect in the myosin light chains that produces primarily papillary muscle hypertrophy.

Dr. Kittleson has also looked at HCM in other breeds, including the American Shorthair. The disease in this breed is also inherited as an autosomal dominant trait; however, the disease commonly is not as severe.

Dr. Kittleson's recommendations for screening Maine Coon cats for breeding depend on the sex of the cat. He recommends that male cats be screened at two years of age or older (because they often have earlier and more severe disease) and female cats be screened later, perhaps at three to four years of age. He stressed that it is very important to have an ultrasonographer who is familiar with the particular components of HCM in Maine Coons as the early changes (such as left papillary muscle hypertrophy) might be missed by the uninformed person.

Resources

Dr. Kittleson's work has been presented at recent veterinary conferences in addition to the Feline Genetic Disease Conference:

1. Meurs K, Kittleson MD, Towbin J, Ware W. Familial systolic anterior motion of the mitral valve and/or hypertrophic cardiomyopathy is apparently inherited as an autosomal dominant in a family of American Shorthair cats. Proceedings of the 15th American College of Veterinary Internal Medicine Forum, Lake Buena Vista, FL, 1997.
2. Kittleson MD, Meurs KM, Kittleson J, Munro M, Liu S, Towbin JA. Heritable characteristics, phenotypic expression, and natural history of hypertrophic cardiomyopathy in Maine Coon cats. Proceedings of the 16th American College of Veterinary Internal Medicine Forum, San Diego, CA, 1998.

The research has also been published in the following journals/books:

1. Kittleson MD. Development and progression of inherited hypertrophic cardiomyopathy in Maine Coon cats (abstract). J Vet Internal Med, Vol 10, No 3, p 165, 1996.
2. Meurs K, Kittleson MD, Towbin J, Ware W. Familial systolic anterior motion of the mitral valve and/or hypertrophic cardiomyopathy is apparently inherited as an autosomal dominant in a family of American Shorthair cats. J Vet Internal Med, Vol 11, No 2, p 138, 1997.
3. Kittleson MD, Kienle RD. Small Animal Cardiovascular Medicine, Mosby, St. Louis, MO, 1998.

AUTOSOMAL DOMINANT GENE

All chromosomes are present in pairs, except for the sex chromosome (X and Y). The chromosomes other than X and Y are called autosomes. A genetic trait that is inherited on the non-sex chromosomes is called autosomal. A genetic trait that is inherited on the sex chromosomes is termed "sex-linked." Most traits are autosomal, including HCM in cats.

The chromosomes contain thousands of genes. Since each autosome is paired, genes on those chromosomes are present in pairs. Each time a body cell divides, the genes multiply with a process of self-copying which is highly accurate. Occasionally, an inexact copy of a gene is made and this is termed a "mutant." Variations from normal types or conditions usually occur as the result of mutations, and this is the case for HCM. When a disease is caused by a mutation in a gene that codes for a structural or functional protein, a mutation in only one copy of the gene ("allele") can produce disease since a full complement of the protein is needed for the affected organ to function normally. When only one allele (either from the mother or father) needs to be affected to cause disease, it is an autosomal dominant trait. Mutations in genes that code for enzymes usually need both alleles (one each from the mother and father) affected since enzyme systems generally have to be suppressed to less than 10% of their normal level to produce an effect (in this case a disease). This is called an autosomal recessive disease. Only one copy of the mutant gene (one allele) is needed to produce HCM in a cat.

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