Page 406 - Feline Cardiology

428 Section P: Cardiac Screening Programs

helpful for testing young kittens in which it may be dif- diogram) at time of breeding could be bred to a
ficult to obtain a blood sample. Additionally, an owner mutation-negative cat. Their lack of clinical disease may
can perform the buccal swabbing at home without suggest that they have a very mild form of the disease or
stressing the cat and mail the swabs directly to the that they just do not show evidence of this adult onset
screening laboratory. clinical disease yet. Therefore these cats should be used
Once the sample is provided to the laboratory it can only if they are exceptional for the breed and they should
be analyzed in a number of ways. The gold standard for be clinically evaluated for the disease by annual echocar-
testing is to perform DNA sequencing for actual visual- diograms. If they develop the clinical disease, they
ization of the mutation. Less reliable but faster assays are should be eliminated from the breeding program. The
available but often have not been fully validated. offspring from the mating of a positive heterozygous
The test results should verify that the cat is negative, and a negative cat should be screened for the mutation,
heterozygous, or homozygous for the mutation. Cats and if possible, a mutation-negative kitten with desir-
that test negative do not have the mutation. This does able traits should be selected to replace the mutation-
not mean that they will not develop hypertrophic car- positive parent in the breeding colony. Over a few
diomyopathy; it simply means that they will not develop generations this will decrease the prevalence of the
the form of the disease caused by the specific genetic disease mutation in the population, and the aim is to do
mutation. Although these mutations have been shown so without altering the genetic makeup of the breed
to be the cause of hypertrophic cardiomyopathy in many significantly. Finally, disease-negative but mutation-
Maine coons and Ragdoll cats, there are some cats that positive cats should be evaluated annually for presence
are echocardiogram-positive for hypertrophic cardio- of disease via echocardiography because they may
myopathy that do not have the specific mutations. develop phenotypic expression of the disease (i.e., left
ventricular hypertrophy) over time.
Recommendations
Over a 2-year period of time, 35% of the Maine OTHER FORMS OF CARDIOMYOPATHY
coon submissions for genetic screening at Washington
State University were found to be positive for the Due to the lower prevalence of both restrictive and
mutation (only 9% of all samples were homozygous- dilated cardiomyopathy and the lack of information
positive) (Fries et al. 2008). Likewise, 28% of the about a familial basis of these diseases in cats, screening
Ragdoll submissions were positive (8% homozygous). programs have not yet been developed. In human beings,
Due to this apparently high prevalence of the mutation both dilated and restrictive cardiomyopathies have been
in both breeds, it would seem to be unwise to recom- well documented as inherited diseases (Kimura 2008;
mend that all cats with these mutations be removed Sen-Chowdhry et al. 2010). Therefore, although there is
from a breeding program since this could result in dra- no known familial component of these diseases in the
matically altering the genetic makeup of these breeds. cat, if they are observed with frequency in a particular
Additionally, it should be emphasized that, because of family or particular breed, a familial etiology should be
the reduced and varied penetrance observed with this strongly suspected and echocardiographic screening
disease, not all cats that have the mutation, particularly should be considered.
if they are heterozygous, will develop a clinical form of
the disease.
REFERENCES
Homozygous cats
Boldface font indicates key references.
Screening form of the disease (particularly Ragdolls), and will cer- Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomyopathy: the
These cats are at a very high risk of developing a severe
Fries R, Heaney AM, Meurs KM. Prevalence of the myosin binding
protein C in Maine coon cats. J Vet Intern Med 2008;22:893–896.
tainly pass on the mutation to offspring since both
copies of their MYBPC3 gene contain the mutation. genetic determinants of clinical disease expression. Nature Clin
Pract Cardiovasc Med 2008;5:158–68.
Homozygous cats should not be used for breeding and Kimura A. Molecular etiology and pathogenesis of hereditary cardio-
should be further evaluated with an echocardiogram. myopathy. Circ J 2008;A:38–48.
Kittleson MD, Meurs KM, Munroe M, et al. Familial hypertrophic
Heterozygous cats cardiomyopathy in Maine coon cats: An animal model of human
disease. Circulation 1999;99:3172–3176.
The heterozygous cat should be carefully evaluated. Cats Lawler DF, Templeton AJ, Monti KL. Evidence for genetic involvement
that have many strong positive breed attributes and are in feline dilated cardiomyopathy. J Vet Intern Med 1993;7:
disease-negative (normal phenotype, i.e., clear echocar- 383–387.