Spinocerebellar Ataxia, early onset, with myokymia and seizures (SCA)

 

Gene: KCNJ10

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:

Jack Russell mutation: Substitution, KCNJ10 gene; c.627 C>G, p.(I209M), exon2

Jack Russell, Parson Russell, Fox Terrier mutation: Insertion, KCNJ10 gene; c.214_215 ins.C

Malinois mutation: Substitution, KCNJ10 gene; c.986 T>C, p.(L329P)

Medical system: Neurological

Breeds: Australian Cattle Dog, Belgian Malinois, Chihuahua, Fox Terrier - Smooth, Fox Terrier - Toy, German Shepherd, Jack Russell Terrier, Parson Russell Terrier, Russell Terrier

Age of onset of symptoms: Around 2 to 6 months

Spinocerebellar ataxia is an early onset progressive neurological disease seen in several of the terrier dog breeds. Clinical signs are seen between 2 to 6 months of age and include incoordination of limbs and loss of balance. The cerebellum, the area of the brain involved with muscle and movement coordination is primarily affected. Spinocerebellar ataxia can be accompanied by episodes of tremor and muscle rigidity that increase with age.  Affected animals are at risk of hyperthermia and in some cases, true epileptic convulsions. Animals suffering from spinocerebellar ataxia are often euthanized before reaching 2 years of age.  In the Belgian Malinois, the disease phenotype is named “Spongy degeneration with Cerebellar Ataxia (SDCA1)”.

 

References:

OMIA link: [2089-9615]

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 37(4):1306-1322. [pubmed/37341581]

Mauri N, Kleiter M, Leschnik M, et al. (2017) A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA1). G3 (Bethesda) 7:663-669.  [pubmed/28007838]

Van Poucke M, Stee K, Bhatti SF, et al. (2017) The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs Eur J Hum Genet. 25:222-226.  [pubmed/27966545]

Rohdin C, Gilliam D, O’Leary CA, et al. (2015) A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in smooth-haired fox terriers with hereditary ataxia and in related breeds. Acta Vet Scand. 57:26. [pubmed/25998802]

Gilliam D, O’Brien DP, Coates JR et al. (2014) A homozygous KCNJ10 mutation in Jack Russell Terriers and related breeds with spinocerebellar ataxia with myokymia, seizures, or both. J Vet Intern Med 28:871-877. [pubmed/24708069]