DEGENERATIVE MYELOPATHY
Definition of DM per the Merck Veterinary Manual:
Degenerative myelopathy of dogs, also called chronic degenerative radiculomyelopathy, is a slowly progressive, non-inflammatory degeneration of the axons and myelin primarily affecting the white matter of the spinal cord. It is most common in German Shepherds, Pembroke Welsh Corgis, Boxers, Rhodesian Ridgebacks, and Chesapeake Bay Retrievers, but is occasionally recognized in many other breeds. The cause is a mutation in the superoxide dismutase1 (SOD1) gene, inherited in an autosomal recessive pattern with incomplete penetrance. It is similar to familial amyotrophic lateral sclerosis in human patients. Pathologically, there is non-inflammatory degeneration of axons in the white matter of the spinal cord, which is most severe in the thoracic region.
Affected dogs are usually >8 yr old and develop an insidious onset of non-painful ataxia and weakness of the pelvic limbs. Spinal reflexes are usually normal or exaggerated, but in advanced cases there is flaccid tetraparesis and hyporeflexia reflecting lower motor neuron involvement. Early cases may be confused with orthopedic disorders; however, proprioceptive deficits are an early feature of degenerative myelopathy and are not seen in orthopedic disease.
Myelography or MRI and CSF analysis are essential to exclude compressive and inflammatory diseases. A DNA test based on the SOD1 gene is available on the Orthopedic Foundation for Animals Web site (http://www.offa.org). Dogs that are homozygous for the mutation are at risk of the disease and will pass one copy of the mutant allele to their offspring. Heterozygotes are at low risk of the disease but have a 50% chance of passing one copy of the mutant allele to each offspring. Homozygous normals are at low risk of the disease and will not pass the mutation to offspring.
There is no specific treatment and no evidence that glucocorticoids, other drugs, or supplements alter the course of the disease. Most dogs are euthanized because of disability within 1–3 yr of diagnosis.
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Further reading and photos:
http://www.caninegeneticdiseases.net/DM/basicDM.htm
More recent findings has led OFA to change their findings.
They now state that they have confirmed cases in dogs with two normal genes N/N and also dogs with one normal and one mutated gene N/A. So at this point in time I no longer consider the test to be as diagnostic and valid as once thought.
I will continue to research and at any point in time when they do find other factors for DM and a more valid test, I will then resume testing, but until then, current DM tests are only small factors of the whole dog.
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From OFA's web site
Explanation of DM DNA Test Results
Normal (N/N)
This dog is homozygous N/N for the mutation that is the most common cause of DM, with two normal copies of the gene. Among the hundreds of dogs studied so far at the University of Missouri, only two dogs with test results of N/N (Normal) have been confirmed to have DM. The N/N (Normal) dog can only transmit the normal counterpart of the common mutation 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. Carriers are far less likely to develop DM, but we have confirmed DM in a few carrier dogs. They may be used carefully in breeding programs to keep their good qualities while reducing risk of DM in future generations.
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). Although almost all dogs in the research study with confirmed DM have had A/A DNA test results, recent evidence suggest that there are other causes of DM in some breeds. In addition, 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.
The researchers at the University of Missouri and the Broad Institute have discovered a gene which is a major risk factor for Degenerative Myelopathy. There are two possible forms (or alleles) of the gene, the normal form (N) and the mutated, or abnormal, form (n). The researchers call these "N" for "Normal" and "A" for "Affected" or "At Risk". Every dog has two alleles, inheriting one from each parent; the combinations can be two copies of the Normal gene (homozygous normal), two copies of the mutated gene (homozygous mutated), or one copy of each gene (heterozygous).
The number of each gene a puppy gets determines its DM risk. The normal gene is dominant, which means that any time a dog has even one normal gene, it is very unlikely to ever develop DM. A dog with two copies of the mutated gene is more likely to develop DM; however this is not a foregone conclusion and there are other factors involved in the expression of the condition.
If a dog has two copies of the normal gene. It will not develop DM and will not produce puppies that will be at risk for DM, regardless of the DM status of the dogs to which it is bred.
If a dog has two copies of the mutated gene (at-risk). It is at risk of developing DM - though not guaranteed to do so. It may produce puppies at risk for DM, if bred to a Carrier or At Risk individual.
An important note: While the actual distribution of genes in an individual litter may stray from the expected (i.e., a clear x carrier breeding may produce 100% clear puppies), over a large number of litters the outcome will meet the expectations. Again, at risk dogs only have a risk of developing DM, they are not guaranteed to do so. Current test results show that about 16% of the breed is at risk, with another 32% carriers - we cannot at this point afford to eliminate all non-clear dogs, or even all at risk dogs, from our breeding programs. Our goal, instead, should be to slowly work reduce the number of at risk dogs - over several generations - and at the same time increase the number of clear dogs. This is something that will likely take decades, not years, for anything like a "nearly rid of DM" status, simply because DM is so widespread, there are so many questions about what "at risk" really means, and heart issues are so much more important and should be where our focus lies for now.
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From OFA's web site:
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.
