What is the human equivalent of Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound)?

OMIA links Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound) to its human counterpart in OMIM (OMIM 601455), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound)

Q: How well studied is Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound) in dogs?

OMIA curates 9 peer-reviewed references for Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound). The full, linked citation list is on this page.

Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound). Autosomal recessive. Observed in 26 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:002120-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human Charcot-Marie-Tooth disease type 4D

This is the canine counterpart of Charcot-Marie-Tooth disease type 4D 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: Charcot-Marie-Tooth disease type 4D (CMT4D) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by a childhood-onset of severe, progressive, demyelinating sensorimotor neuropathy manifesting with distal muscle weakness and atrophy, sensorineural hearing impairment leading to deafness (usually in third decade), severely reduced nerve conduction velocities, and skeletal, especially foot, deformities. Tongue atrophy has also been reported.

In humans it is also called: CMT4D, HMSN4D, HMSNL, NMSL, Charcot-Marie-Tooth disease, type 4D.

MONDO:0011085 OMIM 601455

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.

Summary

The polyneuropathy of juvenile Greyhounds shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth disease in humans.

Clinical features

In Greyhounds, this polyneuropathy becomes evident in juvenile dogs between the ages of three and nine months (Drögemüller et al., 2010). Early clinical features include exercise intolerance (e.g. shaking and collapse after exercise), abnormal gait (e.g. bunny hopping and high stepping), while ataxia, dysphonia and severe muscle atrophy were associated with later clinical features (Drögemüller et al., 2010). Neurological examination may reveal progressive lower motor neuron signs, including progressive ataxia and tetraparesis, delayed proprioceptive paw positioning, distal limb muscle atrophy, hyporeflexia, and inspiratory stridor (high pitched noise during inspiration) (Drögemüller et al., 2010). [IT thanks DVM student Anna Johnston, who provided the basis of this contribution in April 2022.]

Molecular genetics

After genotyping 7 affected Grehounds and 17 normal related Greyhounds with the 50K dog SNP chip, Drögemüller et al. (2010) used homozygosity mapping to identify the candidate 19.5 Mb region on chromosome CFA13. By sequencing the most likely candidate gene in this region, they identified the causative mutation as a 10 bp deletion in exon 15 of the NDRG1 gene (c.1080_1089del10). Bruun et al. (2013) investigated the same disorder in Alaskan Malumutes and reported a novel mutation in the same gene: "The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution." The causative variant in the Alaskan Malamute is c.293G>T.

Pathology

In Greyhounds, a mild to marked decrease in the density of myelinated nerve fibres can be observed. A proportion of the remaining nerve fibres may show a “marked to severe loss of circularity due to para- and internodal crenation” and “outfolded myelin loops at paranodes” (Drögemüller et al., 2010). In approximately 10% of the large, myelinated fibres a mild to marked hyperplasia of axon-Schwann cell network can be seen (Drögemüller et al., 2010). Signs of chronic denervation may be present, including neurogenic atrophy present within some skeletal muscles, de-myelination of fibres within intramuscular nerve branches, as well as perimysial lipid accumulation (Drögemüller et al., 2010). A study of affected Alaskan Malamutes found that these dogs demonstrated more than a 70% reduction in expression of the NDRG1 protein. This suggests that affected animals produce insufficient NDRG1 protein levels for the maintenance of the myelin of Schwann cells, thus resulting in this progressive degenerative polyneuropathy (Skedsmo et al., 2021). [IT thanks DVM student Anna Johnston, who provided the basis of this contribution in April 2022.]

Prevalence

By genotyping archived samples, Jäderlund et al. (2017) showed that "historical and recent phenotypic polyneuropathy cases were carrying the same NDRG1-mutation [c.293G>T; p.Gly98Val]. The pedigree analysis showed that all affected Alaskan malamute cases with polyneuropathy could be traced back to one common ancestor of North American origin."

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 601455 Gene · OMIM 605262

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002120-9615, 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 9.

An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes. · J Vet Intern Med · 2022 · PMID 35019187
Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D. · Neuromuscul Disord · 2021 · PMID 33334662
Re-emergence of hereditary polyneuropathy in Scandinavian Alaskan malamute dogs-old enemy or new entity? A case series. · Acta Vet Scand · 2017 · PMID 28464941
A Gly98Val mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with polyneuropathy. · PLoS One · 2013 · PMID 23393557
Hereditary polyneuropathy in the Alaskan Malamute. · Tierarztl Prax Ausg K Kleintiere Heimtiere · 2012 · PMID 22331326

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 Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound) 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 Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound) looks like in your dog's breed.

Carrier frequency by breed

Top 25 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%

Alaskan Malamute0.89% · n 504

0.89%n 504

American Foxhound<0.1% · n 574

<0.1%n 574

Miniature Pinscher<0.1% · n 658

<0.1%n 658

Australian Cattle Dog<0.1% · n 982

<0.1%n 982

Basset Hound<0.1% · n 990

<0.1%n 990

Japanese Shiba Inu<0.1% · n 2,123

<0.1%n 2,123

Bichon Frise<0.1% · n 1,069

<0.1%n 1,069

Belgian Malinois<0.1% · n 1,186

<0.1%n 1,186

Siberian Husky<0.1% · n 9,035

<0.1%n 9,035

Great Pyrenees<0.1% · n 1,985

<0.1%n 1,985

Yorkshire Terrier<0.1% · n 8,367

<0.1%n 8,367

Poodle Standard<0.1% · n 4,203

<0.1%n 4,203

Pembroke Welsh Corgi<0.1% · n 4,371

<0.1%n 4,371

Australian Shepherd<0.1% · n 2,296

<0.1%n 2,296

Schnauzer Miniature<0.1% · n 4,638

<0.1%n 4,638

n = 42,981 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 Early-Onset Progressive Polyneuropathy (Discovered in the Greyhound) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Alaskan Malamute	0.89%	[0.4%, 2.2%]	504
American Foxhound	<0.1%	[0.0%, 0.8%]	574
Miniature Pinscher	<0.1%	[0.0%, 0.7%]	658
Australian Cattle Dog	<0.1%	[0.0%, 0.5%]	982
Basset Hound	<0.1%	[0.0%, 0.5%]	990
Japanese Shiba Inu	<0.1%	[0.0%, 0.3%]	2,123
Bichon Frise	<0.1%	[0.0%, 0.4%]	1,069
Belgian Malinois	<0.1%	[0.0%, 0.4%]	1,186
Siberian Husky	<0.1%	[0.0%, 0.1%]	9,035
Great Pyrenees	<0.1%	[0.0%, 0.2%]	1,985
Yorkshire Terrier	<0.1%	[0.0%, 0.1%]	8,367
Poodle Standard	<0.1%	[0.0%, 0.1%]	4,203
Pembroke Welsh Corgi	<0.1%	[0.0%, 0.1%]	4,371
Australian Shepherd	<0.1%	[0.0%, 0.2%]	2,296
Schnauzer Miniature	<0.1%	[0.0%, 0.1%]	4,638
Golden Retriever	<0.1%	[0.0%, 0.1%]	12,881
Beagle	<0.1%	[0.0%, 0.1%]	5,292
Pomeranian	<0.1%	[0.0%, 0.1%]	5,294
American Staffordshire Terrier	<0.1%	[0.0%, 0.0%]	42,793
German Shepherd	<0.1%	[0.0%, 0.0%]	15,648
Chihuahua	<0.1%	[0.0%, 0.1%]	4,273
Bulldog Standard	<0.1%	[0.0%, 0.1%]	4,816
Pug	<0.1%	[0.0%, 0.1%]	5,154
Border Collie	<0.1%	[0.0%, 0.1%]	6,714
Shih Tzu	<0.1%	[0.0%, 0.1%]	7,527

Top 25 of 26 well-sampled breeds with at least one observed carrier shown.

240 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:002120-9615.
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:002120-9615, 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:002120-9615 · Donner et al. 2023