Degenerative Myelopathy

Test for Degenerative Myelopathy gene available soon!

Dr. Gary Johnson at the Animal Molecular Genetics Laboratory and Dr. Joan Coates at the Comparative Neurology Program of the University of Missouri and Drs. Claire Wade and Kerstin Lindblad-Toh at the Broad Institute of MIT/Harvard and their colleagues have identified a DNA mutation that is a major risk factor for development of degenerative myelopathy in dogs.

A DNA test will soon be available for breeders and pet owners, along with information about what the test can and cannot tell them. The 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.


Canine Health FoundationThis research was funded by the AKC Canine Health Foundation, American Boxer Charitable Foundation, Pembroke Welsh Corgi Club of America, Rhodesian Ridgeback Club of the United States, French Bulldog Club of America, and French Bulldog Rescue League. To them and the many breeders, pet owners, and veterinarians who assisted, THANK YOU!

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, Pembroke Welsh Corgis, Chesapeake Bay Retrievers 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. It may be that many of these dogs will develop clinical signs as they get older or that the mutation will never manifest in these dogs. Research is still needed to determine the frequency of the mutation in breeds known to have DM (German Shepherd Dogs, Rhodesian Ridgebacks, Pembroke and Cardigan Welsh Corgis, Boxers, Chesapeake Bay Retrievers). In the future, we may identify other risk factors in those dogs that have tested as genetically affected. Wise use of this test can reduce the incidence of dogs at risk for DM in the long-term, particularly if other low frequency risk factors are identified that can more easily be reduced. It is likely to take many generations to reduce the frequency of this disease in breeds with higher frequency of the mutation. By contributing blood samples for testing this mutation, owners will facilitate further study of the disease and the genetic risk factors underlying it.

Additional research funded by participating breed clubs and the AKC Canine Health Foundation will help answer questions that remain. Information about the benefits of this test, testing forms and instructions, and suggestions for using the test to reduce the frequency of DM will soon be available online in the DM section of CANINE GENETIC DISEASES website

 

What is Degenerative Myelopathy?

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.

 


Affected brain
Degenerative myelopathy is a devastating disease causing progressive paralysis in a large number of dog breeds. New research has identified a gene that is associated with a major increase in risk of the disease.

What causes Degenerative Myelopathy?

The exact cause of DM is unknown. Various immune mediated and nutritional theories have been investigated but no definitive cause has been found. It has long been felt that genetics played an important role in the disease since it is common in certain breeds of dogs and follows stereotyped pattern with age of onset and clinical signs. Recent research has identified a mutation in a gene that confers a greatly increased risk of developing the disease.

DM vs Normal

In the section of a spinal cord from a dog who has died of DM (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 througout (Right).

We do know that the disease 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.

How is degenerative myelopathy 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 characteristic degenerative changes in the spinal cord typical for DM and not 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" llink.

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.