How is Acral Mutilation Syndrome (AMS) inherited in dogs?

Acral Mutilation Syndrome (AMS) follows a Autosomal recessive inheritance pattern. It has been observed in 22 of 266 breeds screened in the Sniff Atlas.

What is the human equivalent of Acral Mutilation Syndrome (AMS)?

OMIA links Acral Mutilation Syndrome (AMS) to its human counterpart in OMIM (OMIM 201300, OMIM 223900, OMIM 608654, OMIM 613115, OMIM 614213), the bridge to the deeper human-medicine literature for the same underlying biology.

How well studied is Acral Mutilation Syndrome (AMS) in dogs?

OMIA curates 13 peer-reviewed references for Acral Mutilation Syndrome (AMS). The full, linked citation list is on this page.

Canine Mendelian disease record

Acral Mutilation Syndrome (AMS)

Acral Mutilation Syndrome (AMS). Autosomal recessive. Observed in 22 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:001514-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human Riley-Day syndrome

This is the canine counterpart of Riley-Day 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: A congenital disorder caused by mutations in the IKBKAP gene. It is characterized by damage of the sympathetic and parasympathetic and sensory nervous system.

In humans it is also called: HSAN III, HSAN3, Dysautonomia, Familial, dysautonomia, familial, familial dysautonomia.

MONDO:0009131 OMIM 201300 OMIM 223900

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

As summarised by Plassais et al. (2016): " Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact"

Molecular genetics

"Targeted high-throughput sequencing of [the positional candidate segment] in 4 affected and 4 unaffected dogs" enabled Plassais et al. (2016) to identify 478 variants, only one of which "perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in [the last exon of] a long intergenic non-coding RNAs (lincRNA), GDNF-AS." The authors also reported that " Functional analyses (qRT-PCR, EMSA) confirmed that the mutation alters the binding of regulatory complex, leading to a significant decrease of both GDNF and GDNF-AS mRNA expression levels." Correard et al. (2017) provided additional information about this same variant: "The variant (chr4.g.70,875,561C>T) is located in an intergenic region, 90 kb upstream of GDNF, known to be involved in the regulation of sensory neuron . . . . Using an “in-house” improved annotation of the CanFam 3 genome assembly, the presence of a long non-coding RNA (lncRNA) was detected in the vicinity of GDNF . . . . Interestingly, the variant is located in the last exon of this lncRNA, potentially regulating GDNF."

Prevalence

Correard et al. (2017): "This mutation [chr4.g.70,875,561C>T] is responsible for insensitivity to pain in four sporting dog breeds and it perfectly segregates with the disease in 250 sporting dogs of known clinical status. Moreover, it was not found in any of the 900 unaffected dogs from 130 different breeds."

Inheritance

Correard et al. (2017): "a large pedigree of French spaniels was first drafted; careful analysis of this pedigree revealed a recessive autosomal mode of inheritance, as previously described (Paradis et al. 2005)"

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 201300 Disease · OMIM 223900 Disease · OMIM 608654 Disease · OMIM 613115 Disease · OMIM 614213 Gene · OMIM 600837

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001514-9615, 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 13.

An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. · Genome Biol · 2023 · PMID 37582787
Genetics of inherited skin disorders in dogs. · Vet J · 2022 · PMID 34861369
Canine neuropathies: powerful spontaneous models for human hereditary sensory neuropathies. · Hum Genet · 2019 · PMID 30955094
A spontaneous dog model for a human sensory neuropathy: identification of a mutation in the upstream region of a neurotrophic factor. · Bull Acad Vét Fr · 2017
A point mutation in a lincRNA upstream of GDNF is associated to a canine insensitivity to pain: A spontaneous model for human sensory neuropathies. · PLoS Genetics · 2016 · PMID 28033318

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 Acral Mutilation Syndrome (AMS) 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 Acral Mutilation Syndrome (AMS) looks like in your dog's breed.

Carrier frequency by breed

Top 20 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%10%20%

Old English Sheepdog7.9% · n 423

7.9%n 423

English Cocker Spaniel2.8% · n 580

2.8%n 580

English Springer Spaniel1.6% · n 751

1.6%n 751

Coton De Tulear0.48% · n 104

0.48%n 104

Dachshund Miniature Longhaired0.23% · n 213

0.23%n 213

Newfoundland0.22% · n 463

0.22%n 463

Miniature Pinscher0.15% · n 658

0.15%n 658

German Shorthaired Pointer0.12% · n 1,252

0.12%n 1,252

Cocker Spaniel<0.1% · n 1,881

<0.1%n 1,881

Golden Retriever<0.1% · n 12,881

<0.1%n 12,881

Rottweiler<0.1% · n 4,718

<0.1%n 4,718

Cavalier King Charles Spaniel<0.1% · n 2,243

<0.1%n 2,243

German Shepherd<0.1% · n 15,648

<0.1%n 15,648

Beagle<0.1% · n 5,292

<0.1%n 5,292

Boston Terrier<0.1% · n 3,702

<0.1%n 3,702

n = 50,809 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 Acral Mutilation Syndrome (AMS) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Old English Sheepdog	7.9%	[5.7%, 10.9%]	423
English Cocker Spaniel	2.8%	[1.8%, 4.5%]	580
English Springer Spaniel	1.6%	[0.9%, 2.8%]	751
Coton De Tulear	0.48%	[0.1%, 4.4%]	104
Dachshund Miniature Longhaired	0.23%	[0.0%, 2.2%]	213
Newfoundland	0.22%	[0.0%, 1.2%]	463
Miniature Pinscher	0.15%	[0.0%, 0.9%]	658
German Shorthaired Pointer	0.12%	[0.0%, 0.5%]	1,252
Cocker Spaniel	<0.1%	[0.0%, 0.3%]	1,881
Golden Retriever	<0.1%	[0.0%, 0.1%]	12,881
Rottweiler	<0.1%	[0.0%, 0.1%]	4,718
Cavalier King Charles Spaniel	<0.1%	[0.0%, 0.2%]	2,243
German Shepherd	<0.1%	[0.0%, 0.1%]	15,648
Beagle	<0.1%	[0.0%, 0.1%]	5,292
Boston Terrier	<0.1%	[0.0%, 0.1%]	3,702
Chihuahua	<0.1%	[0.0%, 0.1%]	4,273
Boxer	<0.1%	[0.0%, 0.1%]	4,557
Pomeranian	<0.1%	[0.0%, 0.1%]	5,294
Labrador Retriever	<0.1%	[0.0%, 0.0%]	16,856
American Staffordshire Terrier	<0.1%	[0.0%, 0.0%]	42,793

▸ Also observed in 2 small-sample breeds (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
Cirneco Del Etna	14.3%	[2.6%, 51.3%]	7
Irish Terrier	2.9%	[0.5%, 14.5%]	35

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

Penetrance

From genotype to phenotype

Carrier status is not the same as disease status. Penetrance is the fraction of at-risk dogs that develop the phenotype. The Donner 2023 S4 table tracks this for 1 variant(s) underlying this disease in the cohort.

At-risk dogs evaluated: 3
Phenotype confirmed: 0
Penetrance range: not yet quantifiable

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome is governed by 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:001514-9615.
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:001514-9615, 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:001514-9615 · Donner et al. 2023