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November 20, 2023.      |   Health

Understanding Degenerative Myelopathy in Cavalier King Charles Spaniels: Genetic Factors, Uncertainties, and In-Depth Insights**

Quick ANSWER: NO

The genetic test of the SOD1 gene in cavaliers should determine whether a dog is a genetic carrier of CDM. The disorder is believed to be inherited in an autosomal recessive manner in dogs, meaning that they must receive two copies of the mutated gene -- one from each parent -- to develop the disease.

Summary of below: DM is a genetic disease inherited in an autosomal recessive manner meaning that the dog must receive the mutated gene from both parents to develop the disease. Rarely, this disease may develop in heterozygotes, although the frequency of occurrence is lower. A certain percentage of dogs positive for DM did not exhibit clinical signs in their lifetime.  Cavaliers that are clear of, have a single copy or double copy of DM, DOES NOT solidify developing DM. Today's testing is incomplete in depth  and requires advanced testing to determine with increased certainty.  

Cavalier King Charles Spaniels, cherished for their amiable nature, face the potential challenge of degenerative myelopathy (DM), a progressive spinal cord disease affecting mobility in older dogs. This article explores the genetic intricacies of DM in Cavalier King Charles Spaniels, acknowledging uncertainties in disease development and incorporating insights from recent studies.

**Genetic Basis of DM:**

DM is associated with a mutation in the SOD1 gene, categorized into clear, carrier, or affected with two copies. A study by [ Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000263-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70 ] identified the prevalence of the SOD1 mutation in Cavalier King Charles Spaniels, establishing a genetic framework for understanding DM.

**Uncertainties in Predicting DM:**

While the SOD1 mutation provides insights, it doesn't definitively predict DM development. Research, including a comprehensive study by [see below], highlights that genetic and environmental factors contribute to the variability in disease expression. Not all dogs with the mutation necessarily develop DM, and onset and progression can vary.

**Environmental and Lifestyle Factors:**

In addition to genetics, environmental and lifestyle factors influence DM development. Diet, exercise, and overall health play pivotal roles. Veterinary Organizations recommend holistic canine care and regular veterinary check-ups to mitigate the impact of genetic predispositions.

**DNA Testing Through the Orthopedic Foundation for Animals:**

DM's exact cause is unknown, but a suspected genetic mutation prompts DNA testing. The Orthopedic Foundation for Animals identifies dogs as clear, carriers, or at-risk for DM. This autosomal recessive genetic disease increases the risk of DM, but not all carriers develop the disease. Other genetic and environmental factors contribute.

**University of Sydney Study Insights:**

A study by the University of Sydney reveals DM's clinical rarity and complex inheritance. Testing, especially for the SOD1 mutation, is poorly correlated with DM risk. Recommendations advise against breed-wide breeding strategies based solely on testing. While the SOD1 variant is widespread, clinical cases are few, and in some breeds, DM has never been observed.

**Incompletely Penetrant Autosomal Recessive Disease:**

DM is an incompletely penetrant autosomal recessive disease, typically affecting dogs aged 5 or older. The SOD1:c.118A mutation is commonly tested, and in the Bernese Mountain Dog (BMD) breed, additional testing for SOD1:c.52T is available. Testing identifies animals as clear, at-risk, or carriers, but other factors influence disease development. DM diagnosis requires excluding similar diseases, with definitive diagnosis through post-mortem examination.

**Breed-Specific Mutations and Testing Considerations:**

Research indicates breed-specific mutations, such as the c.52a>T mutation in BMD. Testing for SOD1-A clears the specific mutation associated with it; for a complete genetic picture, SOD1-B testing is necessary. BMD carries either the A or B mutation, not both. If a BMD is at risk for SOD1-A, the test for SOD1-B may not be necessary, and vice versa. If clear or a carrier for one mutation, testing for the other mutation is required.

**Conclusion:**

In concluding our exploration of DM in Cavalier King Charles Spaniels, genetic testing provides valuable insights. The SOD1 mutation alone doesn't guarantee DM development. Holistic care, informed breeding practices, and ongoing research contribute to addressing uncertainties in this beloved breed. Responsible approaches, incorporating genetic and environmental considerations, will shape the well-being of Cavalier King Charles Spaniels in the face of DM complexities.

• Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2794-9. [PubMed: 19188595]
• Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 2007 Nov-Dec; 21(6):1323-31. [PubMed: 18196743]
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• Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci. 2012 Jul 15;318(1-2):55-64. [PubMed: 22542607]
• Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014 Feb 13. doi: 10.1111/jvim.12317. [PubMed: 24524809]
• https://dogwellnet.com/ctp/phenes/100-degenerative-myelopathy/?breeds=107&fbclid=IwAR0zivbihno9HAS_6P1g-wqAy8knRRu8GSOHeJRKwMZNvd6tCPak9am3sRM
• https://omia.org/OMIA000263/9615/
• https://www.pawprintgenetics.com/products/tests/details/87/?breed=56&fbclid=IwAR2xiM98mDczCSnLzwTp8-NRfFNX1SEci66XC4Yuot7bGTtnIuhoeuRgscQ
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Please Note:   A large number of Miniature Poodles, Toy Poodles, and Spaniels are found to carry IVDD.  Please do not be alarmed!!  Poodles and Spaniels ARE NOT affected by IVDD/CDDY like other breeds such as the Corgi or Dachshund.
Geneticists are not recommending we remove carriers of IVDD from our breeding programs because it could result in these breeding pools becoming extremely limited.  At East End Cavaliera we will always strive to breed only the best health and temperaments to provide the healthiest well-adjusted puppies possible, this includes limiting IVDD/CDDY when possible.