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Early-Onset Progressive Polyneuropathy (Discovered in the Alaskan Malamute)

Early-Onset Progressive Polyneuropathy is characterized by the dysfunction and breakdown of multiple nerve types, which causes generalized weakness, and related clinical signs.

Key Signs

Walking difficulties, Exercise intolerance, Voice changes, Progressive severe muscle atrophy, Ataxia, Paralysis of larynx and extremities

Age of Onset

0 to 2 yrs

Juvenile onset

Inheritance

Autosomal Recessive

For autosomal recessive disorders, dogs with two copies of the variant are at risk of developing the condition. Dogs with one copy of the variant are considered carriers and are usually not at risk of developing the disorder. However, carriers of some complex variants grouped in this category may be associated with a low risk of developing the disorder. Individuals with one or two copies may pass the disorder-associated variant to their puppies if bred.

Likelihood of the Condition

High likelihood

At risk dogs are highly likely to show signs of this disease in their lifetime.

What to Do

Here’s how to care for a dog with Polyneuropathy

Partner with your veterinarian to make a plan regarding your dog’s well-being, including any insights provided through genetic testing. If your pet is at risk or is showing signs of this disorder, then the first step is to speak with your veterinarian.

For Veterinarians

Here’s what a vet needs to know about Polyneuropathy

The first observable signs in are voice changes, inspiratory stridor, and pelvic limb weakness with progression to muscle weakness of all four limbs, muscle atrophy, and exercise intolerance beginning about 3 to 19 months of age. Affected dogs are usually reluctant to stand still and climb stairs and eventually progress to tetraparesis. Dogs suffering from this condition have decreased spinal reflexes in all four limbs.

Treatment is supportive care and symptomatic depending on the severity of the dog's clinical signs.

For Breeders

Planning to breed a dog with this genetic variant?

There are many responsibilities to consider when breeding dogs. Regardless of test results it is important that your dog is in good general health and that you are in a position to care for the puppies if new responsible owners are not found. For first time or novice breeders, advice can be found at most kennel club websites.

This disease is autosomal recessive meaning that two copies of the mutation are needed for disease signs to be shown. A carrier dog with one copy of the Polyneuropathy mutation can be safely bred with a clear dog with no copies of the Polyneuropathy mutation. About half of the puppies will have one copy (carriers) and half will have no copies of the Polyneuropathy mutation. Puppies in a litter which is expected to contain carriers should be tested prior to breeding. Carrier to carrier matings are not advised as the resulting litter may contain affected puppies. Please note: It is possible that disease signs similar to the ones caused by the Polyneuropathy mutation could develop due to a different genetic or clinical cause.

Technical Details

Gene NDRG1
Variant G>T
Chromosome 13
Coordinate 29,714,606

All coordinates reference CanFam3.1

References & Credit

Credit to our scientific colleagues:

Drögemüller, C., Becker, D., Kessler, B., Kemter, E., Tetens, J., Jurina, K., … Matiasek, K. (2010). A deletion in the N-MYC downstream regulated gene 1 (NDRG1) gene in greyhounds with polyneuropathy. PLoS ONE, 5(6). View the article

Bruun, C. S., Jäderlund, K. H., Berendt, M., Jensen, K. B., Spodsberg, E. H., Gredal, H., … Fredholm, M. (2013). A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy. PLoS ONE, 8(2), 1–7. View the article

Rentmeister, K., Bilzer, T., Petri, S., Schanen, G., Fehr, M., Distl, O., & Tipold, A. (2012). Hereditary polyneuropathy in the Alaskan Malamute. Tierarztliche Praxis Ausgabe K: Kleintiere - Heimtiere. View the article