Degenerative Myelopathy Exon 2 (SOD1A)

Degenerative Myelopathy Exon 2 (SOD1A)

Degenerative Myelopathy (DM) is a hereditary condition found in various dog breeds. DM causes degeneration of the spinal cord, leading to a decrease in strength and coordination of the hind legs. The mutation for DM is present in nearly all dog breeds, but in many breeds it does not result in clinical symptoms. A DNA test for Degenerative Myelopathy can help reduce the number of affected animals — but in which breeds is this test actually useful?

What is Degenerative Myelopathy?

Degenerative Myelopathy is an hereditary disease that causes damage to the nerves in the spinal cord. As a result, sensation and strength in the hind legs gradually decrease, and other neurological symptoms may occur.

Depending on the breed, DM can be caused by different mutations. In most dog breeds, Degenerative Myelopathy is caused by a mutation in the SOD1 gene, specifically in exon 2 (also known as DM Exon 2 or SOD1A).
In Bernese Mountain Dogs, in addition to this mutation, another mutation in the SOD1 gene, located in exon 1 (DM Exon 1 or SOD1B), can also lead to DM.

The DM Exon 2 mutation is inherited in an autosomal recessive manner with incomplete penetrance, which means that other factors, besides the mutation itself, influence the development of DM.
In Pembroke Welsh Corgis, a modifying risk factor has been identified in the SP110 gene, but for many other breeds, these additional factors are still unknown.

In practice, DM is diagnosed based on likelihood. A definitive diagnosis can only be made post-mortem, by examining a sample of the spinal cord. Therefore, a veterinarian must rule out other possible causes of the symptoms before arriving at a DM diagnosis. The result of a DNA test can support this process, but testing positive (being affected) is not enough on its own to confirm the disease.

Symptoms

Symptoms of DM generally appear when the dog is five years or older. In most breeds, this is around nine years of age, though smaller breeds may be older when symptoms first occur.

Key symptoms include:

• Reduced strength in the hind legs
• Ataxia (wobbly, drunken gait), especially in the hind limbs
• Incontinence (urine and/or feces)
• No pain in the lower back (unlike, for example, with a herniated disc)

The spinal cord damage starts in the lower back and gradually moves upward toward the neck, eventually leading to full-body paralysis.However, most dogs are euthanized before the disease progresses that far. Unfortunately, Degenerative Myelopathy cannot be cured. However, supportive care can improve the quality of life for both the dog and the owner. This includes maintaining muscle mass and practical care tips. Your veterinarian or a certified animal physiotherapist can help guide you through this.

Genetic testing

DM is not curable, but in many cases it can be prevented. By using DNA testing when pairing males and females for breeding, it’s possible to avoid producing puppies with a high risk of developing Degenerative Myelopathy. It’s important to understand that the DM mutation is found in many dog breeds, but only a limited number of these breeds actually develop clinical symptoms of DM. That’s why it’s essential to only draw conclusions from a DM Exon 2 test result in breeds where DM has been proven to occur. Testing for and selecting against DM Exon 2 in breeds without known cases of the disease is usually not meaningful and is therefore discouraged.

An overview of dog breeds where DM is proved to occur (July 2025)

• Airedale Terrier
• American Eskimo Dog
• American Pit Bull Terrier
• American Water Spaniel
• Australian Shepherd
• Bernese Mountain Dog
• Bloodhound
• Border Collie
• Borzoi
• Boxer
• Boykin Spaniel
• Cardigan Welsh Corgi
• Cavalier King Charles Spaniel
• Chesapeake Bay Retriever
• Czechoslovakian Wolfdog
• English Springer Spaniel
• French Bulldog
• German Shepherd Dog
• Glen of Imaal Terrier
• Golden Retriever
• Great Pyrenees
• Hovawart
• Irish Setter
• Jack Russell Terrier
• Kerry Blue Terrier
• Komondor
• Labrador Retriever
• Mioritic Romanian Shepherd Dog
• Nova Scotia Duck Tolling Retriever
• Pembroke Welsh Corgi
• Poodle
• Pug
• Rhodesian Ridgeback
• Rottweiler
• Rough Collie
• Saint Bernard
• Shetland Sheepdog (Sheltie)
• Shiloh Shepherd
• Siberian Husky
• Soft Coated Wheaten Terrier
• Tibetan Terrier
• White Swiss Shepherd Dog
• Wire Fox Terrier

What does autosomal recessive with incomplete penetrance mean?

Some diseases are caused by a gene that doesn’t function properly due to a mutation. These diseases are hereditary. For a recessive mutation, a dog must inherit two copies of the faulty gene — one from the father and one from the mother — in order to develop the disease. If the dog has only one copy, it is considered a carrier. Carriers do not show symptoms of the disease, but they can pass the faulty gene on to their offspring. In the case of autosomal recessive inheritance with incomplete penetrance, even dogs that have two copies of the mutated gene (affected animals) are not guaranteed to develop the disease.
This means that a dog may genetically be affected, but the disease may never actually manifest.

Degenerative Myelopathy Risk Modifier

In Pembroke Welsh Corgi (PWC) risk modifiers have been found in the SP110 nuclear body protein. When present alongside a homozygous SOD1 (DM Exon 2) mutation, the modifiers may increase the risk of developing DM and clinical signs will occur at an earlier age. If the mutation for SOD1A is absent, the presence of SP110 mutations does not have any advantages or disadvantages for the dog. CombiBreed test for all 5 known Risk Modifiers, the results of these tests are reported separately.

Relevant tests

• H673
• H806
• H308
• H158
• H159
• H160
• H161
• H162
• H163