What is the human equivalent of Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever)?

OMIA links Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever) to its human counterpart in OMIM (OMIM 603034), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever)

Q: How well studied is Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever) in dogs?

OMIA curates 5 peer-reviewed references for Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever). The full, linked citation list is on this page.

Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever). Autosomal recessive. Observed in 2 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 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:001928-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human congenital myasthenic syndrome 5

This is the canine counterpart of congenital myasthenic syndrome 5 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: Congenital myasthenic syndrome caused by mutation(s) in the COLQ gene, encoding acetylcholinesterase collagenic tail peptide. It is inherited in an autosomal recessive manner.

In humans it is also called: CMS5, EAD, Cms Ic, COLQ congenital myasthenic syndrome, congenital myasthenic syndrome type 5.

MONDO:0011281 OMIM 603034

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

Affected puppies present with a history of generalised skeletal muscle weakness and fatigue with an onset in the first weeks to months of life (Mignan et al., 2020). As reported by Rinz et al. (2014): "Neurological examination was consistent with a generalized neuromuscular disease with marked short-strided tetraparesis that worsened with exercise. Postural reactions were preserved with the exception of hopping which was diminished in all limbs when the puppies were made to bear full weight. Spinal reflexes including the patellar, cranial tibial, and flexor withdrawals were reduced in all limbs. A pyridostigmine bromide challenge resulted in worsening of muscle weakness." Clinical signs often progress despite treatment, and most reported cases have resulted in death or euthanasia of affected puppies (Mignan et al., 2020). [IT thanks DVM student Lily Cai for contributions in April 2022]

Molecular genetics

Subsequent sequencing by Rinz et al. (2014) of the primary candidate gene (COLQ or LOC608697; see Mapping section above) revealed a causal mutation as "a variant in exon 14 (c.1010T>C) that results in the substitution of a conserved amino acid (I337T) within the C-terminal domain. Both affected puppies were homozygous for this variant, and 16 relatives were heterozygous, while 288 unrelated Labrador Retrievers and 112 dogs of other breeds were wild-type." Sequencing the functional candidate gene COLQ in four affected Golden Retriever puppies from a single breeder enabled Tsai et al. (2020) to identify "a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds."

Pathology

As a result of the COLQ mutation, acetylcholinesterase is anchored to the basal lamina of the neuromuscular junction (NMJ). Measurement of the compound muscle action potential through electrodiagnostic testing after repetitive nerve stimulation shows a decremental response, which is consistent with failure of neuromuscular transmission (Tsai et al., 2020). A NMJ antibody testing for acetylcholinesterase is negative (Mignan et al., 2020). [IT thanks DVM student Lily Cai, who provided the basis of this contribution in April 2022]

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 603034 Gene · OMIM 603033

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001928-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

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 5 (MONDO:0011281).

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.

Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation. · J Vet Intern Med · 2020 · PMID 31769119
Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats. · J Vet Intern Med · 2020 · PMID 32668077
Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms. · Ann N Y Acad Sci · 2018 · PMID 29405353
Myasthenia gravis and congenital myasthenic syndromes in dogs and cats: A history and mini-review. · Neuromuscul Disord · 2016 · PMID 27080328
A COLQ missense mutation in Labrador Retrievers having congenital myasthenic syndrome. · PLoS One · 2014 · PMID 25166616

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 Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

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 Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever) looks like in your dog's breed.

Carrier frequency by breed

Top 2 well-sampled breeds (n ≥ 50)

Maximum carrier 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.

0%1%2%

Labrador Retriever0.22% · n 16,856

0.22%n 16,856

Golden Retriever<0.1% · n 12,881

<0.1%n 12,881

n = 29,737 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 Congenital Myasthenic Syndrome (Discovered in the Labrador Retriever) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Labrador Retriever	0.22%	[0.2%, 0.3%]	16,856
Golden Retriever	<0.1%	[0.0%, 0.1%]	12,881

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

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 carrier 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:001928-9615.
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:001928-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001928-9615 · Donner et al. 2023