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Canine Mendelian disease record

Canine Multiple Systems Degeneration (Discovered in the Chinese Crested Dog; CMSD)

Canine Multiple Systems Degeneration (Discovered in the Chinese Crested Dog; CMSD). Autosomal recessive. Observed in 1 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,664 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001468-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

This is the canine counterpart of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome in people. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Any 3-methylglutaconic aciduria in which the cause of the disease is a mutation in the SERAC1 gene.

In humans it is also called: MEGDEL, MGCA6, 3-methylglutaconic aciduria type VI, 3-MGCA type IV (formerly), 3-MGCA-4 (formerly).

MONDO:0013875 OMIM 614739

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Clinical features

Stee et al. 2023: "This disease has an onset of signs between 9 weeks and 6 months of age. Dogs initially present a mild intention tremor and stiffness in thoracic limb gait, which progresses within 3 to 4 months to severe hypermetric ataxia, spasticity, truncal sway, wide-based stance, delayed postural reactions, and decreased menace response [de Lahunta and Averill, 1976; Deforest et al., 1978; Montgomery and Storts, 1983; O'Brien et al. 2005; de Lahunta et al., 2021]. Signs progress to akinesia, inability to stand and euthanasia by 1 to 2 years of age. Cerebellar atrophy and T2W hyperintensity at the level of the caudate nuclei, putamen, and substantia nigra are visible on MRI in dogs affected for several weeks [O'Brien et al., 2005; de Lahunta et al., 2021]."

Molecular genetics

Stee et al. 2023: "This disease has been associated [in a non-peer reviewed conference proceeding] with 2 distinct breed-specific autosomal recessive variants in SERAC1, respectively a nonsense variant (XM_038654522.1:c.1536G>A (p.[Trp512*])) in the Kerry Blue Terrier and a 4-bp deletion (XM_038654522.1:c.182+1_182+4del) in the Chinese Crested [Guo et al., 2013]."
St Jean et al. (2022) describe three cases of canine multiple system disease in Ibizan hounds. The dogs tested negative for the known SERAC1 variants.

Pathology

Stee et al. 2023: "Macroscopic changes in advanced cases include a decreased cerebellar size (6%-9% of total brain weight) and necrosis of the caudate nuclei, putamen, and substantia nigra. Microscopically, an ischemic degeneration of Purkinje cells is seen first, followed by Purkinje cell and secondary granule cell loss. With chronicity, degeneration occurs in the olivary nuclei, followed by acute bilateral degeneration of caudate nuclei and substantia nigra neurons [de Lahunta and Averill, 1976; Deforest et al., 1978; Montgomery and Storts, 1983; O'Brien et al. 2005; de Lahunta et al., 2021]."

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 614739 Gene · OMIM 614725

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001468-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 14.

  3. Phenotypic and genetic aspects of hereditary ataxia in dogs. · J Vet Intern Med · 2023 · PMID 37341581
  5. Cerebellum. · In: Veterinary Neuroanatomy and Clinical Neurology. A DeLahunta, E Glass, M Kent, eds. 5th ed. Philadelphia: Elsevier · 2021
  6. Canine multiple system degeneration is associated with distinct SERAC1 mutations in two different dog breeds. · Proceedings of the 63rd Annual Meeting of the American Society of Human Genetics; October 22-26, 2013; Boston, USA. · 2013

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Canine Multiple Systems Degeneration (Discovered in the Chinese Crested Dog; CMSD) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Canine Multiple Systems Degeneration (Discovered in the Chinese Crested Dog; CMSD) looks like in your dog's breed.
Carrier frequency by breed

Top 1 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%
Chinese Crested0.25% · n 204
n = 204 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Canine Multiple Systems Degeneration (Discovered in the Chinese Crested Dog; CMSD) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Chinese Crested 0.25% 204

265 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001468-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001468-9615 · Donner et al. 2023