A common question veterinarians often ask when performing genetic testing is what interventions or treatments they should take today to mitigate or prevent future diseases. While the specific answer varies on the condition, let’s take a case of a puppy that tests positive for a genetic mutation associated with dilated cardiomyopathy (DCM).
For a quick review, canine dilated cardiomyopathy is a predominantly inherited and potentially fatal heart condition. In affected dogs, the left ventricle is enlarged or dilated, resulting in a progressive thinning and weakening of the heart wall. This inadequate blood circulation can lead to fluid accumulation in the lungs as well as other parts of the body. Many dogs develop arrhythmias, and ultimately experience decreased cardiac function and output.
Dogs that develop DCM may experience a gradual deterioration leading to death or can be relatively asymptomatic and then die suddenly. Early identification of DCM can be challenging, making testing for genetic risk factors critical for successful outcomes.
In humans, over 60 different genes have been identified that cause inherited cardiomyopathy. In dogs, we have found at least two genetic mutations commonly associated with DCM. The first is the PDK4 gene. (1,2) Dogs with one or two copies of the PDK4 mutation are seven times more likely to develop DCM than dogs without the mutation.
The other mutation, TTN (3), appears to have less risk than PDK4, but the relative risk for developing DCM from the TTN mutation has not been established.
Dogs with both PDK4 and TTN mutations are at the highest risk for developing future dilated cardiomyopathy.
It only takes a single copy of either mutation to develop symptoms, but it’s important to note that not all dogs with either or both of these genes will develop DCM. These mutations are classified as autosomal dominant with incomplete penetrance. While we’re just beginning to understand the myriad of factors that result in this form of heart disease, any dog with a PDK4 or TTN genetic mutation is at risk.
So what do you do with a dog with a PDK4 or TTN mutation? Prepare, Plan, and Peer.
The first thing you need to do is prepare and educate the pet parent about DCM, its symptoms, diagnostics, treatments, and prognoses. If your patient is an at-risk breed, such as Doberman Pinscher, Standard Schnauzer, Great Dane, Boxer, Golden Retriever, Labrador Retriever, or French Bulldog, I highly recommend genetic testing as early as possible.
Next, plan.
If a dog has one or more copies of these genes, consider feeding a diet rich in taurine (4). Taurine is vital for the function of heart muscles, and its deficiency can lead to DCM.
Supplements like L-carnitine and coenzyme Q10 have shown promise in supporting heart health in dogs (4-6). L-carnitine is an amino acid that helps convert fat into energy, which is essential for the heart muscle. Coenzyme Q10 is a powerful antioxidant that can help protect the heart from oxidative stress.
Omega-3 supplementation has long been advised in treating dogs with heart disease (7). Many veterinarians begin supplementing omega-3 fatty acids and other anti-inflammatories in dogs shown to be at risk for developing heart disease.
Finally, veterinarians need to peer or look ahead for the earliest signs of DCM in dogs with these mutations (8). Yearly cardiac examinations are highly recommended. You may recommend annual or bi-annual cardiac ultrasounds beginning around ages three to five. Regular diagnostic tests such as NT-proBNP (9) are also recommended in dogs with PDK4 or TTN mutations.
I hope you’ll consider these recommendations if you have a patient who tests positive for a genetic mutation associated with DCM. If you’d like to learn more about Basepaws Veterinary by Zoetis genetic testing for your clinic, visit basepawsvet.com.
1. Meurs, K.M., Fox, P.R., Norgard, M.M., Spier, A.W., Lamb, A., Koplitz, S.L., & Baunwart, R.D. (2007). A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher. Journal of Veterinary Internal Medicine, 21(5), 1016-1020. doi: 10.1111/j.1939-1676.2007.tb03058.x
2. Meurs, K.M., Lahmers, S., Keene, B.W., White, S.N., Oyama, M.A., Mauceli, E., & Linblad-Toh, K. (2012). A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Human Genetics, 131(8), 1319-1325. doi: 10.1007/s00439-012-1158-2
3. Meurs, K.M., Friedenberg, S.G., Kolb, J., Saripalli, S., Tonino, P., Woodruff, K., Olby, N.J., Keene, B.W., Adin, D.B., Yost, O.L., DeFrancesco, T.C., Lahmers, S., Tou, S., Shelton, G.D., & Granzier, H. (2019). A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death. Human Genetics, 138(5), 515-524. doi: 10.1007/s00439-019-01973-2
4. Sanderson SL. Taurine and carnitine in canine cardiomyopathy. Vet Clin North Am Small Anim Pract. 2006 Nov;36(6):1325-43, vii-viii. doi: 10.1016/j.cvsm.2006.08.010. PMID: 17085238. https://pubmed.ncbi.nlm.nih.gov/17085238/
5. Weng Y, Zhang S, Huang W, Xie X, Ma Z, Fan Q. Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2021 Jan 12;2021:9491615. doi: 10.1155/2021/9491615. PMID: 33521132; PMCID: PMC7817303. https://pubmed.ncbi.nlm.nih.gov/33521132/
6. Druzhaeva N, Nemec Svete A, Tavčar-Kalcher G, Babič J, Ihan A, Pohar K, Krapež U, Domanjko Petrič A. Effects of Coenzyme Q10 Supplementation on Oxidative Stress Markers, Inflammatory Markers, Lymphocyte Subpopulations, and Clinical Status in Dogs with Myxomatous Mitral Valve Disease. Antioxidants (Basel). 2022 Jul 22;11(8):1427. doi: 10.3390/antiox11081427. PMID: 35892628; PMCID: PMC9394267. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394267/
7. Nasciutti PR, Moraes AT, Santos TK, Gonçalves Queiroz KK, Costa APA, Amaral AR, Fernando Gomes Olivindo R, Pontieri CFF, Jeremias JT, Vendramini THA, Brunetto MA, Carvalho ROA. Protective effects of omega-3 fatty acids in dogs with myxomatous mitral valve disease stages B2 and C. PLoS One. 2021 Jul 15;16(7):e0254887. doi: 10.1371/journal.pone.0254887. PMID: 34265016; PMCID: PMC8282066. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282066/
8. Keene BW, Atkins CE, Bonagura JD, Fox PR, Häggström J, Fuentes VL, Oyama MA, Rush JE, Stepien R, Uechi M. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med. 2019 May;33(3):1127-1140. doi: 10.1111/jvim.15488. Epub 2019 Apr 11. PMID: 30974015; PMCID: PMC6524084. https://pubmed.ncbi.nlm.nih.gov/30974015/
9. Dukes-McEwan, J., Garven, K.E., Lopez Alvarez, J., Oliveira, P., Motskula, P.F. and Willis, R. (2022), Usefulness of cardiac biomarker screening to detect dilated cardiomyopathy in Dobermanns. J Small Anim Pract, 63: 275-285. https://doi.org/10.1111/jsap.13455