Hereditary Footpad Hyperkeratosis

Gene: FAM83G

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, FAM83G gene; c.155 G>C, p.(R52P), chr.5.

Medical system: Skin

Breeds: American Staffordshire Terrier/Amstaff, Bedlington Terrier, Bichon Frise, German Hunting Terrier, Irish Terrier, Jagdterrier/German Hunting Terrier, Kromfohrlander, Pug, Welsh Terrier

Age of onset of symptoms: 4 – 5 months.

The footpads of the dog are composed of skin epidermis that is specialized for its weight bearing role.  Hereditary footpad hyperkeratosis (HFH) is a genetic condition involving an abnormal thickening and hardening of the footpads, seen particularly in the Kromfohrländer and the Irish Terrier breeds.  With time the inelastic footpads can develop cracks which can lead to secondary bacterial infections in susceptible animals.  Foot pain and lameness are associated with the condition.  Animals with Hereditary footpad hyperkeratosis also tend to have harder and seemingly faster growing nails as well as duller and softer coats.  Genomic studies identified a mutation of the FAM83G gene as being responsible for the condition.  The exact role of the FAM83G protein product in keratin protein expression and the maintenance of normal footpad epidermis is not known.  DNA tests are available to identify carrier animals to eventually eliminate the mutation and the disease from susceptible breeds.

It is of interest to note that a mutation within another gene (FAM83H) in the FAM83 gene family is responsible for Dry eye, curly coat disease seen in the Cavalier King Charles Spaniel breed.

References:

OMIA link: [1327-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Mauldin EA, Elias PM. (2021) Ichthyosis and hereditary cornification disorders in dogs. Vet Dermatol 32:567-e154. [pubmed/34796560]

Sayyab S, Viluma A, Bergvall K, et al. (2016) Whole-genome sequencing of a canine Family trio Reveals a FAM83G variant associated with hereditary footpad hyperkeratosis. G3 (Bethesda) 6:521-527.  [pm/26747202]

Drögemüller M, Jagannathan V, Becker D, et al. (2014) A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH). PLoS Genet 10:e1004370. [pubmed/24832243]

Binder H, Arnold D, Schelling C, Suter M, Wild P. (2000) Palmoplantar hyperkeratosis in Irish terriers: evidence of autosomal recessive inheritance. J Small Anim Prac 41(2) : 52-55. [pm/10701186]

Contributed by: Maria Gorelik and Rosemarie Laporte, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).