Canine Degenerative Myelopathy (also known as Chronic Degenerative Radiculo Myelopathy) is a progressive disease of the spinal cord in older dogs. The disease has an insidious onset typically between 5 and 14 years of age. It begins with hindquarter weakness, rear limb ataxia (reflex to right foot when turned backwards, slow, or non existent), loss of balance, difficulty rising or laying down, knuckling under while walking, limp tail, rear legs crossing under body, rear leg drag, spinal ataxia, hoarseness of bark, leading to paralysis, and incontinence in the final stages... 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.

Degenerative Myelopathy is a disease causing progressive paralysis in a number of large-sized dog breeds.

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.

In the section of a spinal cord from a dog who has died of DM (as on the left), the degeneration is seen as a loss of the blue color at the edges (arrows) compared with the spinal cord from a normal dog which is blue throughout (as on the right).

This degeneration consists of both demyelization (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 Degenerative Myelopathy 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.

What else can look like Degenerative Myelopathy?

Any disease that affects the dog’s spinal cord can cause similar signs of loss of coordination and weakness. Since many of these diseases can be treated effectively, it is important to pursue the necessary tests to be sure that the dog doesn’t have one of these diseases. The most common cause of hind limb weakness is herniated intervertebral disks. The disks are shock absorbers between the vertebrae in the back. When herniated, they can cause pressure on the spinal cord and weakness or paralysis. Short-legged, long back dogs are prone to slipped disks. A herniated disk can usually be detected with X-rays of the spine and myelogram or by using more advanced imaging such as CT scan or MRI. Other diseases we should consider include tumors, cysts, infections, injuries and stroke. Similar diagnostic procedures will help to diagnose most of these diseases. If necessary, your veterinarian can refer you to a board certified neurologist who can aid in diagnosing Degenerative Myelopathy. A directory to a neurologist near you can be found at American College of Veterinary Internal Medicine website under the "Find a Specialist Near You" link.

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.

DNA Testing Information for Degenerative Myelopathy

Here the very well explained graph of results from VET DNA CENTER when all progeny is tested from one litter of a certain combination, thus even when an At Risk parent is bred to a Carrier Parent, the result can still be 50% or half of the pups born are clear (fortunately). However, the other half will be at risk and not worth the chance to take for any caring and careful breeder.

On the other hand, if a breeder has a top rated male or female which tested AT RISK, (do not panic) then when bred to a NORMAL mate only, this combination will only produce CARRIER offspring, thus this offspring can then be bred to a NORMAL mate, test ALL offspring and choose pups which tested NORMAL only for furthering the breeding program and thereby the breeder can quickly breed out DM in its entirety.

For testing information visit www.vetdnacenter.com

Results	CLEAR N/N Parent	CARRIER A/N Parent	AT RISK A/A Parent
CLEAR N/N Parent	100% Clear	50% Clear 50% Carrier	100% Carrier
CARRIER A/N Parent	50% Clear 50% Carrier	25% Clear 50% Carrier 25% at Risk	50% Carrier 50% at Risk
AT RISK A/A Parent	100% Carrier	50% Clear 50% at Risk	100% at Risk

Normal (N/N)
This dog is homozygous N/N, with two normal copies of the gene. In the seven breeds studied at the University of Missouri in depth so far, dogs with test results of N/N (Normal) have never been confirmed to have DM. This dog can only transmit the normal gene to its offspring, and it is unlikely that this dog or its offspring will ever develop DM.

Carrier (A/N)
This dog is heterozygous A/N, with one mutated copy of the gene and one normal copy of the gene, and is classified as a carrier. In the seven breeds studied at the University of Missouri in depth so far, dogs with test results of A/N have never been confirmed to have DM. While it is highly unlikely this dog will ever develop DM, this dog can transmit either the normal gene or the mutated gene to its offspring.

At-Risk (A/A)
This dog is homozygous A/A, with two mutated copies of the gene, and is at risk for developing Degenerative Myelopathy (DM). The research has shown that all dogs in the research study with confirmed DM have had A/A DNA test results, however, not all dogs testing as A/A have shown clinical signs of DM. DM is typically a late onset disease, and dogs testing as A/A that are clinically normal may still begin to show signs of the disease as they age. Some dogs testing A/A did not begin to show clinical signs of DM until they were 15 years of age. Research is ongoing to estimate what percentage of dogs testing as A/A will develop DM within their lifespan. At this point, the mutation can only be interpreted as being at risk of developing DM within the animal’s life. For dogs showing clinical signs with a presumptive diagnosis of DM, affected (A/A) test results can be used as an additional tool to aid in the diagnosis of DM. Dogs testing At-Risk (A/A) can only pass the mutated gene on to their offspring.

Equivocal
An Equivocal test result indicates that the test results were inconclusive. This is typically the result of poor sample collection. When the test yields an equivocal result, a second punch will be taken from the FTA card and the test rerun. If the second test is still equivocal, the owner will be contacted and asked to submit a new sample.

Guidelines for Breeding DM Dogs Testing Carrier or At Risk

Owners with dogs testing as Carriers (A/N), or At-Risk (A/A) are strongly encouraged to share these results with their attending veterinarian and seek genetic counseling when making breeding decisions.

The “A” (mutated) allele appears to be very common in some breeds. In these breeds, an overly aggressive breeding program to eliminate dogs testing A/A or A/N 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 dog, and can be a trying experience for the owners that care for them. A realistic approach when considering which dogs to select for breeding would be to treat the test results as one would treat any other undesirable trait or fault. Dogs testing At-Risk (A/A) should be considered to have a more serious fault than those testing as Carriers (A/N). Incorporating this information into their selection criteria, breeders can then proceed as conscientious breeders have always done: make their breeding selections based on all the dog’s strengths and all the dog’s faults. Using this approach and factoring the DM test results into the breeding decisions should reduce the prevalence of DM in the subsequent generations while continuing to maintain and improve upon positive, sought after traits.

We recommend that breeders take into consideration the DM test results as they plan their breeding programs; however, they should not over-emphasize the test results. Instead, the test result should be one factor among many in a balanced breeding program.

What DM means to you and your breeding program

If you are a breeder looking to ELIMINATE the possibility of producing AT RISK puppies in your breeding program, then breeding to a CLEAR parent is the first step. By breeding your dog to a CLEAR parent you are ASSURED that EVERY puppy produced from that breeding will be FREE of the risk of developing Degenerative Myelopathy.

For example: Streiter has been DNA tested CLEAR, therefore he will never produce any AT RISK offspring no matter if he is bred to an AT RISK or CARRIER female.

Article By: Joan R. Coates, DVM, MS, Diplomat ACVIM-Neurology

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 five breeds we studied so far (Boxer, Chesapeake Bay Retriever, German Shepherd Dog, Pembroke Welsh Corgi, and Rhodesian Ridgeback), 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 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 life span.

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.

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