Canine Mendelian disease record

Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS)

Q: What is the human equivalent of Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS)?

OMIA links Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS) to its human counterpart in OMIM (OMIM 605809, OMIM 608931, OMIM 616324), the bridge to the deeper human-medicine literature for the same underlying biology.

Q: How well studied is Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS) in dogs?

OMIA curates 10 peer-reviewed references for Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS). The full, linked citation list is on this page.

Congenital Myasthenic Syndrome (Discovered in the Heideterrier; CHRNE-related; CMS). Autosomal recessive. Observed in 9 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,630 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:000685-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human congenital myasthenic syndrome 4A

This is the canine counterpart of congenital myasthenic syndrome 4A 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: A congenital myasthenic syndrome characterized by postsynaptic neuromuscular junction defects, early-onset progressive muscle weakness, and prolonged opening and activity of the acetylcholine receptor channel that has material basis in heterozygous or rarely biallelic mutation in the CHRNE gene on chromosome 17p13.

In humans it is also called: CMS4A, Cms Ia1, congenital myasthenic syndrome type 4A, congenital myasthenic syndrome type Ia1.

MONDO:0011600 OMIM 605809 OMIM 608931

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. 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

Rinz et al. (2015) reported that affected Jack Russell Terrier (JRT) pups appeared normal until 6 weeks of age. "Affected JRT pups showed generalized muscle weakness at 7 weeks of age, walking only briefly for 10–15 short-strided steps before sitting or lying down." Treatment with anticholinesterase drug resulted in temporary improvement of muscle weakness. "Development of drug resistance necessitated euthanasia." Herder et al. (2017): "In a litter of Heideterriers, four out of 11 puppies showed a lack of reflexes and coordination of the front limbs 6 days after birth. Consciousness and general condition of these animals was reported to be normal, and none showed fever. The four affected puppies displayed weakness progressing over the course of the day and peaking at night time. The most severely affected animal showed falling to the side and recumbency, while still being alert and trying to play in this position."

Molecular genetics

By sequencing two positional functional candidate genes, Rinz et al. (2015) concluded that a likely causal mutation in Jack Russell Terriers is "a single base insertion [omia.variant:614, published as c.633_634insC] in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon [p.Gly212Argfs*274]". Herder et al. (2017) investigated a litter of Heideterriers, in which 4 out of 11 puppies showed pronounced muscle weakness. Only one of these puppies was available for genetic analysis. Herder et al. (2017) performed whole genome sequencing and identified a homozygous single nucleotide insertion into the coding sequence of the CHRNE gene (omia.variant:804; XM_014113502.1:c.1436_1437insG). The insertion was predicted to lead to a frameshift and premature stop codon (XP_013968977.1:p.Ser479ArgfsTer14). This variant was absent from the genomes of 274 control dogs. Based on the earlier findings in Jack Russell Terriers and other species, Herder et al. (2017) concluded that "it is plausible that the CHRNE variant may have caused a myasthenia gravis-like disease in the investigated puppy."
Peterson et al. (2024) investigated 2 English Springer Spaniels and their unaffected dam and a Smooth Fox Terrier with congenital myasthenic syndrome. The authors seequenced exons 3–13 of the CHRNE candidate gene and discovered a missense mutation in the English Springer Spaniels (omia.variant:1729; published as chr5:31915101C>A; XP_013968977.2:p.(S503R)) and a 1-bp insertion in the Smooth Fox Terrier that was previously reported in Heideterrier (omia.variant:804) as likely causal variants.

Pathology

Rinz et al. (2015): "No indication of a primary nervous system or muscle disorder was found on post-mortem examination [of affected Jack Russell Terriers]. Occasional groups of atrophic myofibers of both fiber types were noted in cryosections stained with the myofibrillar ATPase reaction. Several end-plates were identified by the esterase reaction product staining, but no AChRs were detectable in serial cryosections by labeling with fluorescent α-bungarotoxin." Herder et al. (2017) reported lack of significant pathological findings in most muscles except for mild lipomatosis musculorum in the M. triceps in a Heideterrier.

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 605809 Disease · OMIM 608931 Disease · OMIM 616324 Gene · OMIM 100725

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000685-9615, 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 10.

Independent CHRNE mutations at serine 503 in English Springer Spaniels and a Smooth Fox Terrier having congenital myasthenic syndrome. · Anim Genet · 2024 · PMID 38853290
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
Frame-shift variant in the CHRNE gene in a juvenile dog with suspected myasthenia gravis-like disease. · Anim Genet · 2017 · PMID 28508416
A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers. · Neuromuscul Disord · 2015 · PMID 26429099
Congenital canine myasthenia gravis: I. Deficient junctional acetylcholine receptors. · Muscle Nerve · 1984 · PMID 6543919

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 Heideterrier; CHRNE-related; CMS) 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 Heideterrier; CHRNE-related; CMS) looks like in your dog's breed.

Carrier frequency by breed

Top 8 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%3%5%

Japanese Shiba Inu0.83% · n 2,122

0.83%n 2,122

Beagle0.74% · n 5,291

0.74%n 5,291

Russell Terrier0.40% · n 239

0.40%n 239

Golden Retriever0.23% · n 12,880

0.23%n 12,880

American Staffordshire Terrier0.17% · n 42,786

0.17%n 42,786

Treeing Walker Coonhound0.15% · n 336

0.15%n 336

Boston Terrier<0.1% · n 3,702

<0.1%n 3,702

German Shepherd<0.1% · n 15,647

<0.1%n 15,647

n = 83,003 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 Heideterrier; CHRNE-related; CMS) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Japanese Shiba Inu	0.83%	[0.5%, 1.3%]	2,122
Beagle	0.74%	[0.5%, 1.0%]	5,291
Russell Terrier	0.40%	[0.1%, 2.3%]	239
Golden Retriever	0.23%	[0.2%, 0.3%]	12,880
American Staffordshire Terrier	0.17%	[0.1%, 0.2%]	42,786
Treeing Walker Coonhound	0.15%	[0.0%, 1.4%]	336
Boston Terrier	<0.1%	[0.0%, 0.1%]	3,702
German Shepherd	<0.1%	[0.0%, 0.0%]	15,647

▸ Also observed in 1 small-sample breed (n < 50)

Frequencies in this section are statistical estimates with wide Wilson 95% confidence intervals (typically >20 percentage points). Treat these as "carriers observed but the true population frequency is not yet measurable" rather than as comparable to the well-sampled entries above.

Breed	Estimate	Wilson 95% CI	n tested
Fox Terrier Smooth	12.5%	[2.6%, 43.2%]	10

257 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:000685-9615.
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:000685-9615, 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:000685-9615 · Donner et al. 2023