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Hereditary Footpad Hyperkeratosis (DH; HFH)
| Acronym: | DH, HFH |
| Gene: | FAM83G |
| Mutation: | c.155G>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Hereditary footpad hyperkeratosis is a skin disorder affecting several dog breeds, such as the Kromfohrlaender, the German Hunting Terrier, the French Mastiff, and the Irish Terrier dog breed. It was originally described for the first time in the Irish Terriers. In general, hyperkeratosis is a condition in which thickening of the outermost layer of the epidermis, known as the stratum corneum, occurs. The condition is associated with abnormally high levels of keratin and the term ”hyperkeratosis” literally means ”above normal levels of keratinized tissue”. Hereditary Footpad Hyperkeratosis was in previous years referred to as Digital Hyperkeratosis (DF). Hereditary Footpad Hyperkeratosis (HFH) is also known as ”corny feet”. In contrast to idiopathic hyperkeratosis, which develops for unknown reasons, HFH is caused by a mutation in a specific gene.
The outermost layer of the epidermis, the stratum corneum, is an essential barrier of the body against the environment. The part of the dog’s feet that is in contact with the ground is covered by the palmoplantar epidermis, with a layer of dead cells, specially structured to bear the strongest mechanical forces of the entire skin. In the layers of palmoplantar epidermis protein keratin 9 is expressed. Mutations of this protein have been associated with epidermolytic palmoplantar keratoderma, a genetic skin disorder in humans. In dogs under normal circumstances, the surface level of dead cells is constantly worn out as the dog exercises. The constant levels of thickness of the outermost layer are being maintained by replacement with more keratinized cells produced by underlying, living, cells. The occurrence of cracking of the pads within the inelastic keratinized layer is common, but it appears on the surface, without reaching into the underlying sensitive layers. In a healthy dog, painful cracks can be due to external causes, such as exposure to wet and dry conditions, chemicals, or zinc deficiency. They usually heal spontaneously, while this is not the case with hereditary footpad hyperkeratosis (HFH). The first symptoms usually develop at 4-5 months of age and they affect all footpads. The pad surface becomes very hard and develops cracks. Affected dogs have problems walking on irregular surfaces and may become unable to walk due to the pain walking causes them. Cracks can be sites of infections, making the pain severer. Nails are very hard and seem to grow faster. Symptom severity can vary among dogs, or even between the pads of one dog, and due to that, diagnostics can sometimes be hard to perform and DNA testing is the best option for disorder identification.
Hereditary Footpad Hyperkeratosis HFH is caused by a mutation in the gene expressing the FAM83G protein. The FAM83 protein family consists of 8 known members FAM83A – FAM83H. Mutation in the FAM83G gene in human patients is associated with hypocalcified amelogenesis imperfecta. In dogs, another mutation in the FAM83H causes a disorder called ”dry eye curly coat syndrome” in the Cavalier King Charles Spaniel dogs. Hereditary Footpad Hyperkeratosis HFH is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show HFH symptoms. When mating two carriers (heterozygotes) at conception each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Currently, there is no cure for HFH. Excessive keratinized tissue on pads can be carefully trimmed away by the veterinarian and cracks can be softened by using a hydration product. Secondary infections need to be cured with antibiotics.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Drogenmuller M., Jagannathan V., Becker D., Drogenmuller C., Schelling C, et al. (2014) A Mutation in the FAM83G Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH). PLoS Genet 10(5): e1004370. doi:10.1371/journal.pgen.1004370