Degenerative Myelopathy (DM dog)
In degenerative myelopathy (DM), the long spinal cord nerves slowly degenerate. As a result, symptoms develop such as reduced perception of stimuli, weakness of movement, loss of fine motor skills and finally complete paralysis of the hind and forehand.
Some time ago, a risk factor for the development of DM was discovered, a mutation in the superoxide dismutase 1 gene (SOD1 gene). SOD is an important free radical inhibitor in cells and prevents free radicals from causing significant damage to the genetic material and cell integrity. If this fails due to the mutation, the cells are increasingly damaged.
The disease occurs in many breeds, large dogs are particularly affected. The inheritance is autosomal recessive.
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- The first signs are a reduced perception of stimuli and weakness of movement.
- Loss of fine motor skills (often unilateral) manifests itself as wrong footing or stumbling
- Expansion of the weakness and disorders in the reflexes
- Initially, the hind legs are more affected (until complete paralysis); as the disease progresses, the front legs are also affected.
- The respiratory, throat and pharyngeal muscles are affected, so that breathing and swallowing difficulties occur.
- General immobility in the final stage can occur within a year.
- Degenerative myelopathy (DM) causes a slowly progressive death of the long spinal cord nerves.
- The long spinal cord nerves connect the brain with the periphery and conduct the signals for sensation (sensory) and movement.
- The death of the nerves causes a disorder of sensory perception and movement.
- Symptoms usually appear in the older dog (5-14 years).
- The death of the nerve cells does not cause pain.
- Some time ago, a risk factor for developing DM was discovered, a mutation in the superoxide dismutase 1 gene (SOD1 gene).
- SOD is an important free radical scavenger in cells and prevents free radicals from causing significant damage to genetic material and cell integrity.
- The interception of these damaging molecules is particularly important for nerve cells, as they no longer divide, which would allow damaged cells to be replaced in other cell types.
- If the SOD1 gene is mutated, SOD fails and nerve cells are increasingly damaged.
- A comparison was made with human amyotrophic lateral scelrosis, which is also due to such an SOD1 defect.
The medical history with a slowly progressive course and absence of pain is indicative. A definite diagnosis can only be made after death by patho-histological examination of spinal cord sections.
Differential diagnosis excludes other causes of spinal cord dysfunction. These include:
- Prolapsed intervertebral discs or
- Bony protrusions in the spinal canal or spinal column
- Deformities of the spinal cord
It is problematic if there is compression of the nerve exits of the spinal cord (cauda equina compression syndrome) and/or hip joint dysplasia. DM is then no longer recognisable.
The genetic test for the SOD1 mutation is not a differential diagnostic method.
A mutation in the gene SOD1 is described as a risk factor for the disease (Awano et al. 2009).
Its distribution in individual dog breeds was presented by Zeng et al. in 2014.
Across all breeds, the mean frequency of the risk mutation was 37.5%.
Genotype and Lab Report
Inheritance: autosomal recessive
→ The risk of developing DM is increased if both copies of the gene (dm/dm) are affected by the mutation. Dogs with only one copy of the causative mutation (N/dm) are clinically healthy carriers.
As things stand, dogs that are homozygous for the mutation have a statistical risk of 1 in 135 of developing DM; animals that are free of the mutation, or are heterozygous carriers, have a risk of 1 in 6172.
N/N = genetically normal
The dog has no predisposition to DM and therefore cannot pass it on to offspring.
N/dm = one carrier
The dog is clinically healthy. The causative SOD1 mutation is passed on to 50% of the offspring.
dm/dm = affected
The dog has an increased risk of developing DM. The SOD1 mutation is passed on 100% to the offspring.
- Carrier animals can be bred to normal animals (N/dm x N/N). Before the offspring are used in breeding, they should be tested to see if they are normal or carriers.
- When breeding with two carriers (N/dm x N/dm), there is a 25% chance for each puppy to inherit two copies of the mutation (dm/dm) and thus an increased risk of developing DM. This should be taken into account when planning the breeding.
Awano, T., 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 106:2794-9, 2009. Pubmed reference: 19188595. DOI: 10.1073/pnas.0812297106.
Coates, JR., March, PA., Oglesbee, M., Ruaux, CG., Olby, NJ., Berghaus, RD., O'Brien, DP., Keating, JH., Johnson, GS., Williams, DA.: Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med 21:1323-31, 2008. Pubmed reference: 18196743. DOI: 10.1892/07-059.1
Ivansson, E.L. et al.: Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. Proc Natl Acad Sci U S A 113:E3091-100, 2016. Pubmed reference: 27185954. DOI: 10.1073/pnas.1600084113.
Zeng, R., Coates, J.R., Johnson, G.C., Hansen, L., Awano, T., Kolicheski, A., Ivansson, E., Perloski, M., Lindblad-Toh, K., O'Brien, D.P., Guo, J., Katz, M.L., Johnson, G.S.: Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med 28:515-21, 2014. Pubmed reference: 24524809. DOI: 10.1111/jvim.12317.
E. Manz(1) und M. Krawczak(2) (2017): Bewertung des DNA-Tests zur SOD1-Mutation für die Prognose der Degenerativen Myelopathie (DM).
| 1 = Generatio Sol. GmbH, Blumenstr. 49, 69115 Heidelberg | 2 = Institut für Medizinische Informatik und Statistik, Christian-Albrechts-Universität zu Kiel.
Further information is available at: Online Mendelian Inheritance in Animals.