Ataxia, spinocerebellar

Gene: SLC12A6

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.

Mutation: Deletion/insertion, SLC12A6 gene; c.178_181 delins CATCTCACTCAT, p.(M60H fs STOP 14)

Medical system: nervous

Breeds: Belgian Malinois

Age of onset of symptoms: 3 to 6 months

Hereditary ataxia in the Belgian Malinois is a genetic neurodegenerative disease characterized mainly by progressive spinocerebellar ataxia as a result of the slow development of lesions within the cerebellum and cervical spinal cord. Clinical signs include an absence of patellar reflexes, muscular weakness of the pelvic limbs (paraparesis) and a slightly palmigrade position of the forelegs, shown by the animal’s carpals being closer to the ground than normal. Sedation-induced muscle contractions of the tongue and eyelids are present in some Malinois and are similar to those of myokymia, a condition described by involuntary muscle tremors at rest.  By about 2.5 to 3 years of age, affected dogs are often no longer able to bear weight or walk, i.e. are non-ambulatory.

References:

OMIA link: [2279-9615]

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]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Van Poucke M, Stee K, Sonck L, et al. (2019) Truncating SLC12A6 variants cause different clinical phenotypes in humans and dogs. Eur J Hum Genet 27:1561-1568.  [pubmed/31160700]

Contributed by : Justine La Penna and Maria Anna Barg, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).