Genetic panel of the Russell terrier (and terrier of the Russell group, including Parson Russell terrier) that groups three distinct hereditary recessive neurodegenerative diseases: juvenile brain disease (JBD), late-onset ataxia (LOA) and spinocerebellar ataxia with myokymia and/or seizures (SCA/SAMS). JBD (PITRM1) and SCA/SAMS (KCNJ10) have a consolidated molecular basis; the association of LOA with CAPN1 is described but disputed. The genetic tests are specific for each variant.

Russell terrier, Parson Russell terrier and the Russell group of terriers. SCA due to KCNJ10 has also been described in the Smooth Fox Terrier and Toy Fox Terrier (Rohdin 2015). JBD due to PITRM1 is solidly documented in the Parson Russell terrier. No reliable carrier frequencies are published for the European population (limited data).

- JBD: epileptic seizures starting between 6-12 weeks, myelinopathy and rapid neurological deterioration; death or euthanasia within months
- LOA: symmetric ataxia starting between 6-12 months, slowly progressive, with hypermetria of the pelvic limbs
- SCA/SAMS: spinocerebellar ataxia with myokymia, neuromyotonia and/or seizures; onset around 2-12 months
- Histopathological findings: cerebellar and/or spinal cord degeneration depending on the form

The hereditary ataxias of the Russell group were differentiated into several molecular entities. Gilliam and colleagues (2014) identified the KCNJ10 c.627C>G mutation in the Jack Russell terrier and related breeds causing spinocerebellar ataxia with myokymia and/or seizures (SAMS), and Rohdin and colleagues (2015) confirmed it in the Smooth Fox Terrier. Forman and colleagues (2013) associated CAPN1 c.344G>A (p.Cys115Tyr) with a late-onset spinocerebellar ataxia (LOA) in the Parson Russell terrier, but Gast and colleagues (2016) did not reproduce the association and its causal role remains disputed. Hytönen and colleagues (2021) characterized the juvenile brain disease (JBD) of the Parson Russell terrier due to an in-frame deletion in PITRM1 (c.175_180del).

- Genotype breeding animals for PITRM1, CAPN1 and KCNJ10 before mating
- Do not mate two carriers for the same variant
- A carrier can be mated to a clear animal and the offspring intended for breeding must be tested
- Exclude affected homozygotes from breeding
- After a confirmed clinical case, do not repeat the parental mating and notify the buyer
- Warn that SCA of the Russell group may have more than one molecular basis (locus heterogeneity)

Differential diagnosis between the three forms: age of onset and the presence of myokymia/seizures help. The causal role of CAPN1 c.344G>A is disputed (Forman 2013 proposed it; Gast 2016 did not validate it), so a positive CAPN1 result should be interpreted with caution. JBD (PITRM1) debuts with early seizures and brain deterioration; SAMS (KCNJ10) with ataxia and myokymia around 2-6 months. A clear result for one variant does not rule out the other two.

1. Gilliam D et al. A homozygous KCNJ10 mutation in Jack Russell Terriers and related breeds with spinocerebellar ataxia with myokymia, seizures, or both. J Vet Intern Med. 2014;28(3):871-877. PMID: 24708069.
2. Forman OP et al. Missense mutation in CAPN1 is associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed. PLoS One. 2013;8(5):e64627. PMID: 23741357.
3. Hytönen MK et al. In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration. Hum Genet. 2021;140(11):1593-1609. PMID: 33835239.
4. Rohdin C et al. 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. 2015;57:26. PMID: 25998802.
5. Gast AC et al. Genome-wide association study for hereditary ataxia in the Parson Russell Terrier and DNA-testing for ataxia-associated mutations in the Parson and Jack Russell Terrier. BMC Vet Res. 2016;12:225. PMID: 27724896.
6. OMIA:002089-9615 (ataxia cerebelar, KCNJ10-related); OMIA:001820-9615 (ataxia espinocerebelar, CAPN1-related); OMIA:002324-9615 (epilepsia mitocondrial, PITRM1-related).