Hereditary neurodegenerative disease of the Nova Scotia duck tolling retriever that combines cerebellar degeneration and inflammatory myositis. It appears between 10 weeks and 6 months of age as progressive ataxia with hypermetria and, in many cases, muscle weakness and episodes of collapse. Serum creatine kinase (CK) is markedly elevated (3-25 times the upper limit) and MRI shows bilateral lesions in the cerebellum and masticatory muscles. The prognosis is poor and affected dogs are usually euthanised.

Specific to the Nova Scotia duck tolling retriever. Estimated allele frequency of 3.6% in the European population and 1.3% in the North American one, with carrier frequencies of 7.1% and 2.7%, respectively. No cases have been described outside the breed.

- Generalised ataxia and hypermetria with onset between 10 weeks and 6 months\n- Muscle weakness and exercise intolerance\n- Episodes of collapse and a stiff or 'hopping' gait\n- Marked elevation of serum creatine kinase (3-25 × ULN)\n- Mild spontaneous activity on EMG of distal muscles\n- Bilateral lesions in cerebellar and masticatory nuclei on MRI\n- Lymphohistiocytic myositis on muscle biopsy

The cerebellar degeneration and myositis complex (CDMC) was characterised in two related litters of Nova Scotia duck tolling retriever with four affected puppies. Whole-genome sequencing of one affected dog against 565 controls revealed a private missense variant in SLC25A12 (c.1337C>T; p.Pro446Leu), a gene encoding the mitochondrial aspartate/glutamate transporter. The variant co-segregated with the phenotype in both litters with a monogenic recessive pattern. The estimated allele frequencies were 3.6% in the European cohort and 1.3% in the North American one. The p.L349P variant of the same gene described by Shelton et al. (2019) corresponds to an inflammatory myopathy of the Dutch Shepherd, not to CDMC of the NSDTR.

- Test breeding animals before mating; prioritise lines with a neurological or muscular history\n- Do not cross two carriers: 25% risk of affected homozygotes\n- A carrier can be mated with a clear animal; offspring intended for breeding must be tested\n- Progressively replace carriers with clear offspring without narrowing the gene pool\n- In the face of a puppy with ataxia and elevated CK, confirm the genotype before planning matings of the parents

The differential diagnosis must include immune-mediated inflammatory myopathies, muscular dystrophies and other cerebellar ataxias of the NSDTR. Elevated CK and MRI with bilateral lesions in the cerebellum and masticatory muscles point towards CDMC. Muscle biopsy shows invasive lymphohistiocytic fibre myositis without evidence of an infectious agent. Do not confuse with the p.L349P variant (Dutch Shepherd).

1. Christen M et al. 2022, SLC25A12 missense variant in Nova Scotia Duck Tolling Retrievers affected by cerebellar degeneration-myositis complex (CDMC). Genes (Basel) 13(7):1223. PMID: 35886006. 2. Shelton GD et al. 2019, A mutation in the mitochondrial aspartate/glutamate carrier leads to a more oxidizing intramitochondrial environment and an inflammatory myopathy in Dutch Shepherd dogs. J Neuromuscul Dis 6(4):485-501. PMID: 31594244 (variante p.L349P, Pastor holandés). OMIA:002294-9615.