Degenerative Myelopathy

What is DM?

Degenerative myelopathy is a progressive disease of the spinal cord in older dogs. The disease has an insidious onset typically between 8 and 14 years of age. It begins with a loss of coordination (ataxia) in the hind limbs. The affected dog will wobble when walking, knuckle over or drag the feet. This can first occur in one hind limb and then affect the other. As the disease progresses, the limbs become weak and the dog begins to buckle and has difficulty standing. The weakness gets progressively worse until the dog is unable to walk. The clinical course can range from 6 months to 1 year before dogs become paraplegic. If signs progress for a longer period of time, loss of urinary and fecal continence may occur and eventually weakness will develop in the front limbs. Another key feature of DM is that it is not a painful disease.

What causes degenerative myelopathy?

Degenerative myelopathy begins with the spinal cord in the thoracic (chest) region. If we look under the microscope at that area of the cord from a dog that has died from DM, we see degeneration of the white matter of the spinal cord. The white matter contains fibers that transmit movement commands from the brain to the limbs and sensory information from the limbs to the brain.  This degeneration consists of both demyelination (stripping away the insulation of these fibers) and axonal loss (loss of the actual fibers), and interferes with the communication between the brain and limbs. Recent research has identified a mutation in a gene that confers a greatly increased risk of developing the disease.

How is DM clinically diagnosed?

Degenerative myelopathy is a diagnosis of elimination. We look for other causes of the weakness using diagnostic tests like myelography and MRI. When we have ruled them out, we end up with a presumptive diagnosis of DM. The only way to confirm the diagnosis is to examine the spinal cord under the microscope when a necropsy (autopsy) is performed. There are degenerative changes in the spinal cord characteristic for DM and not typical for some other spinal cord disease.

How do we treat degenerative myelopathy?

There are no treatments that have been clearly shown to stop or slow progression of DM. Although there are a number of approaches that have been tried or recommended on the internet, no scientific evidence exists that they work. The outlook for a dog with DM is still grave. The discovery of a gene that identifies dogs at risk for developing degenerative myelopathy could pave the way for therapeutic trials to prevent the disease from developing. Meanwhile, the quality of life of an affected dog can be improved by measures such as good nursing care, physical rehabilitation, pressure sore prevention, monitoring for urinary infections, and ways to increase mobility through use of harnesses and carts.

Testing for degenerative myelopathy:

The collaborative efforts of Dr Joan Coates and Dr Gary Johnson and associates at the University of Missouri and Dr Kirsten Lindblad-Toh and Dr Claire Wade and associates at the Broad Institute at MIT/Harvard have resulted in identification of a mutation that is a major risk factor for the development of Degenerative Myelopathy in many breeds of dogs.

The DNA test for DM is now available through the Orthopedic Foundation for Animals (OFA). This test clearly identifies dogs that are clear (have 2 normal copies of the gene), those who are carriers (have one normal copy of the gene and one mutated copy of the gene), and those who are at much higher risk for developing DM (have 2 mutated copies of the gene). However, having two mutated copies of the gene does not necessarily result in disease. Dogs that have clinical signs or a presumptive diagnosis of DM have tested as genetically affected. A relatively high percentage of dogs in several breeds (including Boxers, Chesapeake Bay Retrievers. Pembroke Welsh Corgis, and Rhodesian Ridgebacks) have the predisposing mutation. It is important to note that there are a large number of dogs that have tested as genetically affected, but are reported as clinically normal by their owners. Information in the RESEARCH section of this website outlines continued and ongoing research that seeks to understand what triggers development of clinical symptoms in some, but not all dogs at risk.

Understanding the DNA test for degenerative myelopathy:

We have discovered a gene which is a major risk factor for degenerative myelopathy (DM). In that gene, the DNA occurs in two possible forms (or alleles). The “G” allele is the predominant form in dog breeds in which DM seldom or never occurs; you can think of it as the “Good” allele. The “A” allele is more frequent in dog breeds for which DM is a common problem; you can think of it as the “Affected” allele.

Summary: “A” allele is associated with DM; “G” allele is not associated with DM.

Since an individual dog inherits two alleles (one from the sire and one from the dam) there are three possible test results: two “A” alleles; one “A” and one “G” allele; and, two “G” alleles.
Summary: Test results can be A/A, A/G, or G/G.

In the seven breeds we studied so far (Boxer, Chesapeake Bay Retriever, German Shepherd Dog, Pembroke Welsh Corgi, Cardigan Welsh Corgi, Rhodesian Ridgeback, and Standard Poodle), dogs with test results of A/G and G/G have never been confirmed to have DM. Essentially all dogs with DM have the A/A test result. Nonetheless, many of the dogs with an A/A test result have not shown clinical symptoms of DM. Dogs with DM can begin showing signs of disease at 8 years of age, but some do not show symptoms until they are as old as 15 years of age. Thus, some of the dogs who have tested A/A and are now normal may still develop signs of DM as they age. We have, however, found a few 15-year-old dogs that tested A/A and are not showing the clinical symptoms of DM. Unfortunately, at this point we do not have a good estimate of what percent of the dogs with the A/A test result will develop DM within their lifespan.

Summary: Dogs that test A/G or G/G are very unlikely to develop DM. Dogs that test A/A are much more likely to develop DM. Our research will now focus on how many A/A dogs can survive to old age without developing DM and why.

The “A” allele is very common in some breeds. In these breeds, an overly aggressive breeding program to eliminate the dogs testing A/A or A/G might be devastating to the breed as a whole because it would eliminate a large fraction of the high quality dogs that would otherwise contribute desirable qualities to the breed. Nonetheless, DM should be taken seriously. It is a fatal disease with devastating consequences for the dogs and a very unpleasant experience for the owners who care for them. Thus, a realistic approach when considering which dogs to select for breeding would be to consider dogs with the A/A or A/G test result to have a fault, just as a poor top-line or imperfect gait would be considered faults. Dogs that test A/A should be considered to have a worse fault than those that test A/G. Dog breeders could then continue to do what conscientious breeders have always done: make their selections for breeding stock in light of all of the dogs’ good points and all of the dogs’ faults. Using this approach over many generations should substantially reduce the prevalence of DM while continuing to maintain or improve those qualities that have contributed to the various dog breeds.

Summary:

We recommend that dog breeders take into consideration the DM test results as they plan their breeding programs; however, they should not over-emphasize this test result. Instead, the test result is one factor among many in a balanced breeding program.
 
This article has been approved to publish by the University of Missouri staff.  For additional info please go to the following websites: 

www.CanineGeneticDiseases.net
www.OFFA.org