Is there a genetic test for Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier)?

Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier) is associated with the KRT10 gene. Where a validated DNA test for the causal variant is available, it can identify dogs carrying the variant before breeding. Per-breed variant frequency figures are published in the Sniff Atlas (242,665 dogs screened).

What is the human equivalent of Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier)?

OMIA links Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier) to its human counterpart in OMIM (OMIM 113800, OMIM 607602, OMIM 609165), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier)

Q: How well studied is Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier) in dogs?

OMIA curates 10 peer-reviewed references for Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier). The full, linked citation list is on this page.

Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier). Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,665 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:001415-9615
Inheritance: Autosomal recessive
Linked gene: KRT10
Human counterpart: In humans, this gene is KRT10. OMIM 148080 In people, KRT10 appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 0.88). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms. In people, variants in the KRT10 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human epidermolytic hyperkeratosis 1

Dogs with this condition carry a change in KRT10. In people, changes in the same gene cause epidermolytic hyperkeratosis 1. 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.

MONDO:0700249 OMIM 113800 OMIM 607602

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.

Summary

This disorder is a form of ichthyosis.

Clinical features

"Adult [Norfolk Terrier] dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility." (Credille et al., 2005) Kiener et al. (2023) investigated an "11-month-old male Chihuahua ... with severe skin lesions gradually progressing from 5 months of age. Clinical examination revealed severe, multifocal hyperkeratosis, mainly affecting paw pads, axillas and the skin around the anus, lips and eyes ... ."

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Credille et al. (2005) documented the molecular basis of this disorder in a family of Norfolk terrier dogs: "Affected dogs were homozygous for a single base GT>TT change in the consensus donor splice site of intron 5 in [the gene for keratin 10] KRT10. . . . . The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region." Kiener et al. (2023) investigated an affected Chihuahua. Analysis of whole genome sequencing data identified a likely de-novo heterozygous missense variant (Chr9:21814695G>A, XM_038547368.1:c.437G>A, XP_038403296.1:p.(Arg146His)) in the KRT10 candidate gene. "Heterozygous variants affecting human Arg156, homologous to canine Arg146, have been described in several human patients with epidermolytic hyperkeratosis ... ."

Pathology

"Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes." (Credille et al., 2005) Kiener et al. (2023) reported "marked epidermal hyperplasia and orthokeratotic hyperkeratosis with hypergranulosis, forming papillary projections on the skin surface" in skin biopsies of an affected Chihuahua.

Inheritance

Mode of inheritance is described as recessive in Norfolk Terriers and as likely dominant in a single Chihuahua (Credille et al., 2005; Kiener et al., 2023).

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 113800 Disease · OMIM 607602 Disease · OMIM 609165 Gene · OMIM 148080

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001415-9615, 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.

Development of cost-effective PCR-RFLP methods for screening Mendelian disorders in Chihuahua dogs. · F.U. Vet. J. Health Sci. · 2026
Heterozygous KRT10 missense variant in a Chihuahua with severe epidermolytic ichthyosis. · Anim Genet · 2023 · PMID 37332248
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. · Genome Biol · 2023 · PMID 37582787
Inheritance of monogenic hereditary skin disease and related canine breeds. · Vet Sci · 2022 · PMID 36006348
Genetics of inherited skin disorders in dogs. · Vet J · 2022 · PMID 34861369
Ichthyosis in dogs—Congenital dermatologic disorder. · Folia Veterinaria · 2021

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 Epidermolytic Hyperkeratosis (Discovered in the Norfolk Terrier) 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:001415-9615.
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.

Gene page: KRT10, cited identity, disease associations, and the human-gene bridge.
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:001415-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated July 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001415-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)