Myxomatous disease of the mitral valve (MMVD)

MMVD is a progressive degenerative disease affecting the mitral valve and gradually leading to pathological changes. It has been diagnosed in a wide range of breeds (Cavalier King Charles Spaniel, Dachshund, Miniature Poodle, Yorkshire Terrier). MMVD is the most common acquired cardiovascular disease in dogs (it is reported that up to 75% of canine cases of heart disease are associated with MMVD). However, the highest prevalence of MMVD is clearly in the Cavalier King Charles Spaniel breed. Compared to other dog breeds, this breed is at increased risk of developing the disease at a very early age and often with a very severe course. Progressive degenerative changes occur slowly and over time lead to congestive heart failure.

Symptoms usually appear around the age of six. They begin with a heart murmur, which is the primary symptom indicating the development of mitral valve disease. Pathological changes in the valve lead to backflow of blood, volume overload of the left atrium, and, in advanced stages, to fluid accumulation in the lungs. This results in impaired breathing, shortness of breath, and coughing. In the final stage, the above symptoms lead to heart failure

MMVD is a multifactorial and polygenic disease. However, only one mutation in the NEBL 3 gene associated with the possible development of MMVD has been identified so far. Research into other possible variants is still ongoing.

The detected mutation in the NEBL3 gene (chr2:11,979,724) G/A increases the risk of MMVD and is inherited in an autosomal recessive manner. Individuals who inherit the mutated gene from both parents have an increased risk of developing the disease. These individuals are designated P/P (positive/positive). Carriers of the mutated gene, designated N/P (negative/positive), have the mutated gene from only one parent and are at no risk of developing MMVD. However, they pass on the risk mutation to their offspring. A healthy individual has the N/N genotype.

When two heterozygotes (N/P) mate, theoretically 25% of their offspring will be healthy, 50% will be carriers, and 25% will inherit both mutated genes from their parents and will have an increased risk of developing MMVD. Crossbreeding a healthy individual (N/N) and a carrier (N/P) will theoretically result in 50% carriers and 50% healthy individuals.

Mead SE, Beijerink NJ, O’Brien M, Wade CM. Genetic Variants at the Nebulette Locus Are Associated with Myxomatous Mitral Valve Disease Severity in Cavalier King Charles Spaniels. Genes. 2022; 13(12):2292. https://doi.org/10.3390/genes13122292

Axelsson, Erik, et al. "The genetic consequences of dog breed formation—accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels." PLoS genetics 17.9 (2021): e1009726.