Canine Mendelian disease record

Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer)

Q: How well studied is Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer) in dogs?

OMIA curates 9 peer-reviewed references for Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer), including the landmark study "Whole-genome sequencing of a canine Family trio Reveals a FAM83G variant associated with hereditary footpad hyperkeratosis.". The full, linked citation list is on this page.

Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer). Autosomal recessive. Observed in 7 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,663 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:001327-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

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 Drögemüller et al. (2014): "Hyperkeratosis of the foot pads is noticed by the owners of both breeds at 4–5 months of age and involves all footpads. With time horny protrusions appear on the rims of the footpads and the pad surface becomes hard and develops cracks . . . . Affected animals avoid walking on irregular surfaces and may go lame. The nails of affected dogs are very hard and seem to grow faster. We noticed a duller, less wiry, softer coat on an affected Kromfohrländer . . . . Similar clinical symptoms were noted on 5 HFH affected Irish Terriers."

Molecular genetics

Comparison of sequence in the positional candidate region, from whole-genome sequencing of an affected Kromfohrländer at 23.5x coverage, with relevant sequence from 46 non-affected dogs from other breeds identified the causal mutation as "a missense variant (c.155G>C) in the FAM83G gene encoding a protein with largely unknown function. It is predicted to change an evolutionary conserved arginine into a proline residue (p.R52P)". The causality of this variant was confirmed by genotyping of this mutation in other affected and normal dogs. In a proof-of-concept project to detect a likely causal mutation without GWAS, Sayyab et al. (2016) reported the first use of whole-genome sequencing of a family trio (affected offspring and its two non-affected parents) which enabled them to confirm the causal mutation reported by Drögemüller et al. (2014): "527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G>C (p.R52P) was found to be concordant in eight additional cases and 16 healthy Kromfohrländer dogs." Makri et al. (2021) report affected Bedlington Terriers that were homozyvous for the FAM83G:c155G>C variant.

Human analog

OMIA links this condition to the human gene record in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Gene · OMIM 615886

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001327-9615, 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.

★
Whole-genome sequencing of a canine Family trio Reveals a FAM83G variant associated with hereditary footpad hyperkeratosis. · G3 (Bethesda) · 2016 · PMID 26747202
Why is this an OMIA Landmark paper? It is the first report in an OMIA species of the use of whole-genome sequencing of a family trio (sire, dam and offspring) to identify a likely causal variant. In this case, the variant identification was actually a confirmation of a previously-discovered likely causal variant. [FN thanks Hamutal Mazrier for bringing this discovery to his attention]
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
Bedlington terriers diagnosed with familial footpad hyperkeratosis are carriers of an FAM83G mis-sense variant. In: 32nd European Veterinary Dermatology Congress (online) 16–16 September 2021 Abstracts. · Veterinary Dermatology · 2021
Ichthyosis and hereditary cornification disorders in dogs. · Vet Dermatol · 2021 · PMID 34796560
FAM83G/Fam83g genetic variants affect canine and murine hair formation. · Exp Dermatol · 2019 · PMID 29963719

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 Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer) 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 Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer) looks like in your dog's breed.

Carrier frequency by breed

Top 4 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%

Kromfohrlander8.4% · n 197

8.4%n 197

Bichon Frise<0.1% · n 1,069

<0.1%n 1,069

American Staffordshire Terrier<0.1% · n 42,793

<0.1%n 42,793

Pug<0.1% · n 5,154

<0.1%n 5,154

n = 49,213 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 Hereditary Footpad Hyperkeratosis (Discovered in the Irish Terrier and Kromfohrländer) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Kromfohrlander	8.4%	[5.3%, 13.1%]	197
Bichon Frise	<0.1%	[0.0%, 0.4%]	1,069
American Staffordshire Terrier	<0.1%	[0.0%, 0.0%]	42,793
Pug	<0.1%	[0.0%, 0.1%]	5,154

▸ Also observed in 3 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
Bedlington Terrier	13.6%	[3.2%, 42.9%]	11
German Hunting Terrier	3.8%	[0.4%, 28.3%]	13
Welsh Terrier	2.4%	[0.2%, 19.2%]	21

259 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: 3
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:001327-9615.
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:001327-9615, 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:001327-9615 · Donner et al. 2023