Polyneuropathy

 

Gene: NDRG1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Malamute mutation: Substitution, NDRG1 gene; c.293 G>T, p.(G98V), exon5

Greyhound mutation : Deletion, NDRG1 gene; c.1080_1089 del.10, p.R361S fs STOP 60)

Medical system: Neurologic

Breed: Alaskan Malamute, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Shepherd, Basset Hound, Beagle, Belgian Malinois, Bichon Frise, Border Collie, Chihuahua, English Bulldog, French Bulldog, German Shepherd, Golden Retriever, Great Pyrenees, Greyhound, Miniature Pinscher, Pembroke Welsh Corgi, Pomeranian, Poodle - Standard, Pug, Schnauzer - Miniature, Shiba Inu, Shih Tzu, Siberian Husky, Yorkshire Terrier

Age of onset of symptoms: 3 to 19 months

Polyneuropathy is a progressive neuromuscular genetic disease seen in the young animal and presenting with variable severity depending on the individual. Clinical signs include intolerance to exercise, strident breathing sounds and paralysis of the larynx resulting in a change in vocalization. Symptoms progress to include muscle atrophy and weakness of the limbs and spine. There is loss of coordination of the hind limbs followed by the forelimbs, making it difficult for the animal to walk. In severe cases, the affected animal will be euthanized for humanitarian reasons.

 

References:

OMIA links:  [1292-9615] , [2120-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Hultman J, Jäderlund KH, Moe L, et al. (2022) Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes. J Vet Intern Med 36:672-678.  [pubmed/35019187]

Skedsmo FS, Espenes A, Tranulis MA, et al. (2021) Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. Neuromuscul Disord 31:56-68.  [pubmed/33334662]

Jäderlund KH, Rohdin C, Berendt M, et al. (2017) Re-emergence of hereditary polyneuropathy in Scandinavian Alaskan malamute dogs-old enemy or new entity? A case series.  Acta Vet Scand. 59(1):26.  [pubmed/28464941]

Bruun CS, Jaderlund KH, Berendt M, et al. (2013) A Gly98Val mutation in the N-Myc downstream regulated gene 1 (NDRG1) in Alaskan malamutes with polyneuropathy.  PLOS ONE 8(2):e54547. [pubmed/23393557]

Rentmeister K, Bilzer T, Petri S, et al. (2012)  Hereditary polyneuropathy in the Alaskan Malamute. Tierarztl Prax Ausg K Kleintiere Heimtiere. 40(1):26-34. [pubmed/22331326]

Braund KG, Shores A, Lowrie CT, et al. (1997) Idiopathic polyneuropathy in Alaskan malamutes. J Vet Intern Med. 11(4):243-9. [pubmed/9298480]