Degenerative Myelopathy (SOD1 gene)

Degenerative myelopathy (DM) is a progressive and debilitating neurological disease, which causes degeneration of the spinal cord. One of the genes affected is SOD1.

Symptoms

The first symptoms of the disease usually appear at an advanced age, around 8 years of age. The disease begins with symptoms such as reduced reflexes, proprioceptive upper motor neuron spasticity and lack of coordination in hind leg mobility. Over time, the condition progresses to a generalized loss of muscle mass in the limbs, followed by paraplegia and, finally, flaccid tetraparesis. In addition, neurological problems such as difficulty in eating, increased sensitivity to stimuli, and difficulties in controlling urination and defecation may arise.

Disease Management

Although there is no known cure for MD in dogs, there are treatment options focused on controlling symptoms, relieving muscle pain and improving the animal's quality of life. Physical therapy is a useful tool for maintaining muscle strength and mobility. In addition, some studies have shown that aminocaproic acid and N-acetylcysteine supplements can slow the progression of the disease and improve the dog's long-term health.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Degenerative myelopathy is a neurodegenerative disease of the spinal cord that damages the white matter, responsible for the transmission of nerve impulses. A causative mutation, c.118G>A, has been identified in exon 2 of the SOD-1 (superoxide dismutase 1) gene. Notably, some dogs homozygous for the c.118G>A variant have no clinical symptoms of MD, suggesting incomplete penetrance or the existence of other loci involved in the disease. A second causative mutation (c.52A>T) has been identified in the SOD-1 gene that is currently not included in our test. Pfahler et al. (2014) observed that the presence of one copy of the c.118G>A mutation and another copy of the c.52A>T mutation (compound heterozygosity) generates a similar risk of MD as the c.118G>A variant in homozygosity. According to the study by Zeng et al. (2014), it was concluded that the c.118G>A variant is widespread among the canine population, while the c.52A>T mutation is rare and may be limited only to the Bernese Mountain Dog breed.

Most affected breeds

Belgian Shepherd
Boxer
Chesapeake Bay Retriever
German Shepherd Dog
Hovawart
Pembroke Welsh Corgi
Rhodesian Ridgeback

Bibliography

Awano T, Johnson GS, Wade CM,et al. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2794-9.

Pfahler S, Bachmann N, Fechler C,et al. Degenerative myelopathy in a SOD1 compound heterozygous Bernese mountain dog. Anim Genet. 2014 Apr;45(2):309-10.

Wininger FA, Zeng R, Johnson GS,et al. Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense mutation. J Vet Intern Med. 2011 Sep-Oct;25(5):1166-70.

Zeng R, Coates JR, Johnson GC,et al. Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med. 2014 Mar-Apr;28(2):515-21.