What is the human equivalent of Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS)?

OMIA links Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS) to its human counterpart in OMIM (OMIM 254210), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS)

Q: How well studied is Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS) in dogs?

OMIA curates 6 peer-reviewed references for Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS). The full, linked citation list is on this page.

Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS). Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,664 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier: OMIA:002072-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human congenital myasthenic syndrome 6

This canine condition is studied as a natural model of congenital myasthenic syndrome 6 in people; it is not the same as a human congenital myasthenic syndrome 6 diagnosis. Studying dogs can move medicine forward for everyone; the canine disease remains the subject.

In people, the disease is described as: Congenital myasthenic syndrome caused by mutation(s) in the CHAT gene, encoding choline O-acetyltransferase. It is inherited in an autosomal recessive manner.

In humans it is also called: CMS1A, CMS6, CMSEA, FIM, CHAT congenital myasthenic syndrome.

MONDO:0009689 OMIM 254210

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 2026-08-27.

Summary

Congenital myasthenic syndrome is a neuromuscular disorder of Old Danish Pointing Dogs characterized by transient paralysis after exercise. The causative mutation in ChAT causes reduced presynaptic acetylcholine synthesis. A genetic test is available. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Clinical features

Affected dogs can run normally for 5 to 30 minutes, but then begin to take shorter and shorter strides. Eventually, they fall down with flexed legs. The signs disappear after several minutes of rest, but will recur if exercise is continued. These dogs have no detectable antibodies against acetylcholine receptors, and have normal numbers of acetylcholine receptors at the neuromuscular junction. In contrast to dogs with myasthenia gravis, neither edrophonium nor neostigmine has any effect on the clinical signs (Proschowsky et al., 2007).

Molecular genetics

The causative mutation is a G to A substitution in exon 6 of the Choline O-acetyltransferase gene (ChAT). This changes an amino acid codon from valine to methionine (Proschowsky et al., 2007).

Pathology

The clinical signs are caused by a presynaptic defect that reduces synthesis of acetylcholine in affected dogs (Proschowsky et al., 2007).

Prevalence

Reported cases have been limited to Denmark.

History

Congenital myasthenic syndrome was first recognized in Old Danish Pointing Dogs in 1977 (Flagstad, 1982).

Control

The population of Old Danish Pointing Dogs in Denmark is small, and importation of for breeding purposes is not allowed. All dogs should be tested prior to breeding. To avoid production of affected dogs, but allow for population expansion and gradual eradication of the mutation, carrier dogs may be bred with homozygous normal dogs (Proschowsky et al., 2007).

Genetic testing

A test is available to Danish breeders of Old Danish Pointing Dogs (Proschowsky et al., 2007).

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 254210 Gene · OMIM 118490

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002072-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

OMIA curates the disease definition, the clinical description and the reference list. The cross-species disease identity is Monarch's. Sniff renders these and adds the breed-level frequencies, the plain-language summary, and a stated reason wherever a number is missing.

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as congenital myasthenic syndrome 6 (MONDO:0009689).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (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.

Presynaptic congenital myasthenic syndromes: understanding clinical phenotypes through in vivo models. · J Neuromuscul Dis · 2023 · PMID 37212067
An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats. · J Vet Intern Med · 2020 · PMID 32668077
Identification of a mutation in the CHAT gene of Old Danish Pointing Dogs affected with congenital myasthenic syndrome. · J Hered · 2007 · PMID 17586598
Development of the electrophysiological pattern in congenital myasthenic syndrome · Progress in Veterinary Neurology · 1993
A new hereditary neuromuscular disease in the dog breed "Gammel Dansk Honsehund". Genetic investigations. · Hereditas · 1982 · PMID 7201985

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.

Your breed

See what Congenital Myasthenic Syndrome (Discovered in the Old Danish Pointer; CMS) looks like in your dog's breed.

Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. 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.

Scope of this record

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 variant frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

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:002072-9615.
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.

Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:002072-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated August 27, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:002072-9615 · Donner et al. 2023