Inherited, progressive neurodegenerative disorder of the Chinese Crested dog, with degeneration of the cerebellum, caudate nucleus and substantia nigra. It appears in puppies or young dogs and progresses to inability to remain standing and euthanasia. The cause is loss of function of the SERAC1 gene. It is a test complementary to, not a substitute for, clinical examination.

Rare disease. Documented in the Chinese Crested dog and in the Kerry Blue Terrier (with a different variant). No carrier frequencies have been published; limited data.

- Intention tremor and gait stiffness, with onset between 9 weeks and 6 months
- Ataxia and progressive hypermetric gait, spasticity and wobbling
- Wide stance and slowed postural reactions
- Decreased menace response
- Progression to akinesia and inability to remain standing
- Cerebellar atrophy and T2 hyperintensity in the caudate, putamen and substantia nigra on MRI
- Fatal course; euthanasia usually between 1 and 2 years

CMSD was first described in the Kerry Blue Terrier and was mapped to a region of canine chromosome 1. In 2024, Zeng and colleagues sequenced whole genomes of affected dogs of both breeds and identified biallelic variants of SERAC1: a nonsense variant in the Kerry Blue and a 4 bp deletion in the splice acceptor site of exon 4 in the Chinese Crested, which causes skipping of exon 4. The genotype-phenotype concordance was complete and the crosses confirmed the recessive inheritance.

- Test Chinese Crested breeding animals for the SERAC1 c.182+1_182+4del variant before breeding
- Do not mate two carriers: 25 % affected homozygotes
- A carrier may be mated with a clear dog; the offspring intended for breeding must be tested
- Exclude affected animals and known carriers from breeding
- Do not extrapolate the Kerry Blue variant to the Crested or vice versa: they are different variants

Differential diagnosis with other degenerative cerebellar ataxias and with cerebellar atrophies of juvenile onset. MRI guides by the involvement of the caudate, putamen and substantia nigra. Canine CMSD is a model of human disorders due to SERAC1 deficiency. Confirm the variant by sequencing before any reproductive decision.

1. Zeng R et al. 2024, Canine multiple system degeneration associated with sequence variants in SERAC1. Genes (Basel) 15(11):1378. PMID: 39596578. 2. O'Brien DP et al. 2005, Genetic mapping of canine multiple system degeneration and ectodermal dysplasia loci. J Hered. PMID: 15958791. OMIA:001468-9615.