Group of genodermatoses characterised by painful keratotic thickening of the plantar pads of dogs, with fissures and crusts that limit walking. Within the common phenotype, at least two distinct molecular bases are recognised: in the Kromfohrländer, Irish Terrier (and Bedlington Terrier) the cause is a mutation in FAM83G (classic HFH), whereas in the Dogue de Bordeaux the cause is a mutation in KRT16 (focal non-epidermolytic palmoplantar keratoderma, FNEPPK1). In both forms the inheritance is autosomal recessive.

Affected breeds: Dogue de Bordeaux, Kromfohrländer, Irish Terrier (and Bedlington Terrier). In the Dogue de Bordeaux, the study of 334 dogs showed 245/306 clear and 61/306 carriers among the unaffected, suggesting a carrier frequency close to 20%. For the Kromfohrländer and Irish Terrier no large series with reliable allele frequency have been published; consider "limited data".

- Progressive thickening and hardening of the plantar pads, visible from 4-6 months (Kromfohrländer/Irish Terrier) or between 10 weeks and 1 year (Dogue de Bordeaux)\n- Horny protrusions at the edges of the pads ("corny feet")\n- Painful fissures of the pad that bleed and become superinfected\n- Lameness and reluctance to walk on uneven surfaces\n- Harder and faster-growing nails in the Kromfohrländer and Irish Terrier\n- In some Kromfohrländer, a duller and less harsh coat (syndromic phenotype)\n- No associated nasal involvement in these forms

Digital hyperkeratosis of the Irish Terrier was described clinically decades ago and was traditionally considered a monogenic recessive trait. In 2014, Drögemüller and colleagues performed GWAS in the Kromfohrländer (13 cases and 29 controls) and in the Irish Terrier (10 cases and 21 controls), mapped the locus to chromosome 5 and, through whole-genome resequencing of an affected dog, identified a single missense variant in FAM83G: c.155G>C, p.Arg52Pro. The variant segregated perfectly in more than 500 dogs and was not found in 288 dogs of other breeds. Later studies showed that affected Bedlington Terrier dogs share the same variant, supporting a common ancestor. Independently, Plassais and colleagues described in 2015 the form specific to the Dogue de Bordeaux, mapped to the type I keratin cluster on chromosome 9: a complex indel mutation in KRT16 that introduces a premature stop codon (p.Glu392*) and would abolish the function of keratin 16. It is the canine model of human KRT16-related FNEPPK.

- Test breeding animals with the breed-specific test before mating: FAM83G c.155G>C for the Kromfohrländer and Irish Terrier; KRT16 indel for the Dogue de Bordeaux\n- Do not mate two carriers of the same variant: 25% risk of affected homozygotes\n- A carrier can be mated with a clear animal; the offspring intended for breeding must be tested and clear animals preferentially selected, progressively replacing the carrier without narrowing the gene pool\n- Exclude homozygous affected animals from breeding\n- In a dog with thickened and fissured pads, confirm the diagnosis with biopsy (orthokeratotic hyperkeratosis in HFH-FAM83G; in FNEPPK1-KRT16 conoidal "church spire" papillomatosis and parakeratotic hyperkeratosis) and, above all, with genetic testing\n- Do not spread the allele to lines where it is not present; remember that the FAM83G variant is shared by several related breeds

Differential diagnosis with other causes of digital hyperkeratosis: hereditary nasal parakeratosis of the Labrador due to SUV39H2 (also affects the nasal planum, not in HFH/FNEPPK1); epidermolytic ichthyosis of the Norfolk Terrier (affects generalised skin, not only the pads); digital hyperkeratosis due to leishmaniasis, pemphigus foliaceus, zinc-responsive dermatosis (Nordic breeds) or nutritional deficiency. Biopsy helps, but molecular testing is decisive. Remember that the Dogue de Bordeaux has its own molecular basis (KRT16) and will not benefit from a FAM83G test: always use the correct test for the breed. Palliative management with emollients, topical keratolytics (urea, salicylic acid) and early treatment of superinfections.

1. Drögemüller M, Jagannathan V, Becker D, Drögemüller C, Schelling C, Plassais J, Kaerle C, Dufaure de Citres C, Thomas A, Müller EJ, Welle MM, Roosje P, Leeb T. 2014. A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH) (PLoS Genet) (PMID 24832243).
2. Plassais J, Guaguère E, Lagoutte L, et al. 2015. A spontaneous KRT16 mutation in a dog breed: a model for human focal non-epidermolytic palmoplantar keratoderma (FNEPPK) (J Invest Dermatol) (PMID 25521457).
3. OMIA:001327-9615 (Hyperkeratosis, palmoplantar, FAM83G-related) y OMIA:002088-9615 (Palmoplantar keratoderma, nonepidermolytic, focal 1; KRT16).