Test Detail

Keratinocyte genodermatosis of the Norfolk terrier due to a mutation in the KRT10 gene, which encodes keratin 10 of the suprabasal spinous layer. Homozygous dogs present generalized pigmented hyperkeratosis with epidermal fragility (epidermolysis), which manifests as adherent scales and erosions after minor trauma. It is the first keratinocyte mutation confirmed in a non-human species and the first described recessive form of epidermolytic hyperkeratosis, whereas in humans the usual pattern is dominant.

Affected breed: Norfolk terrier. It has been described in one extensive family; no reliable carrier frequency figures have been published in the breed, so it should be considered "limited data". A heterozygous missense variant in KRT10 has been described in a Chihuahua with severe epidermolytic ichthyosis (Kiener et al. 2023): a distinct and dominant form, not relevant to the Norfolk terrier.

- Generalized pigmented hyperkeratosis (greyish-brownish) from young adulthood\n- Thick adherent scales on the trunk and, above all, in friction areas\n- Erosions and blisters after minor trauma (epidermal fragility)\n- Predominant non-palmoplantar involvement (unlike other keratodermas)\n- Histologically: epidermolysis with orthokeratotic hyperkeratosis; on EM, abnormal filament aggregation in the spinous layer\n- Heterozygous dogs clinically normal

Human epidermolytic hyperkeratosis has been known for decades to be caused by dominant mutations in KRT1 and KRT10. The group of Credille, Barnhart and Dunstan described in 2005 a recessive form in an extensive family of Norfolk terriers: adult dogs with generalized pigmented hyperkeratosis and epidermal fragility. Light microscopy showed epidermolysis with hyperkeratosis and, on electron microscopy, decreased tonofilaments and abnormal filament aggregation in suprabasal spinous keratinocytes. Molecular analysis identified a single-base substitution in the splice donor site of intron 5 of KRT10 (GT→TT, c.1125+1G>T) that activates cryptic splice sites and leads to transcripts with premature stop codons and loss of K10 protein expression. It is the first keratinocyte defect confirmed outside the human species.

- Test Norfolk terrier breeding animals with the KRT10 c.1125+1G>T test before mating, especially in lines with a history of hyperkeratosis or from the described family\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier can be mated to a clear animal; offspring intended for breeding should be tested and, ideally, progressively replace the carrier with clear descendants without narrowing the gene pool\n- Exclude affected homozygous animals from breeding\n- In an adult Norfolk terrier with generalized hyperkeratosis and erosions, suspect EHK and confirm with biopsy and genetic testing before any reproductive decision\n- Remember the recessive nature: unlike the dominant human form, heterozygotes are healthy and can be kept in breeding if properly managed

Differential diagnosis with other canine ichthyoses (PNPLA1 of the Golden retriever, NIPAL4 of the American Bulldog, SLC27A4 of the Great Dane, TGM1 of the Jack Russell terrier) and with demodicosis, leishmaniosis, endocrinopathies (hypothyroidism) and acquired ichthyoses. Electron microscopy, if available, is highly indicative (abnormal filament aggregation in the suprabasal spinous layer). Management is palliative: emollients, topical keratolytics, control of superinfections and protection of the skin against trauma. There is no curative treatment; prevention is based on pre-breeding genetic testing.

1. Credille KM, Barnhart KF, Minor JS, Dunstan RW. Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs. Br J Dermatol 153:51-58, 2005.. PMID: 16029326
2. Kiener S et al. 2023, variante missense heterocigota de KRT10 en un Chihuahua con ictiosis epidermolítica grave (PMID 37332248)