Sometimes referred to as “Epidermolytic Ichthyosis”
Facts
- What does KRT1 stand for? Keratin 1.
- What does the KRT1 gene do? Encodes Keratin1, which contributes to the structural framework of keratinocytes.
- Clinical significance of mutation? Epidermal hyperkeratosis.
About KRT1–pEDD
Skin disease caused by KRT1 mutations is known as KRT1-pEDD or Epidermolytic ichthyosis(EI), Epidermolytic Hyperkeratosis, or Striate palmoplantar keratoderma. However, not all cases of EI are caused by KRT1 mutations, as some are caused by defects in KRT 10.2 The disease is very rare and is estimated to have a prevalence of 1.0 per 200,000.1 EI is passed down from a parent to their offspring in an autosomal dominant inheritance pattern.1 However, spontaneous mutation occurs in approximately 50% of all cases where there is no family history of the disease.4 This means that it only takes one copy of the mutated KRT1 gene from one parent to cause the disease. The parent who has EI has a 50% chance of passing the mutated KRT1 gene in each pregnancy. Genetic testing is necessary to determine whether symptoms of EI are caused by a mutation in the KRT1 gene.3,4
Symptoms of KRT1
Signs of EI appear in early infancy as reddened skin, extensive blistering, and some loss of skin in affected areas. As the child grows older, ichthyotic traits with rippled keratosis and skin scaling begin to appear on flexural surfaces.3,4 Over time, the blistering becomes less prominent, however, EI may lead to issues with blistering after a skin infection or trauma. Some individuals with EI may develop palmoplantar keratoderma.3 Hyperkeratotic lesions are defined papules that appear as thickening of the outer layer of skin. EI can be clinically classified into two subtypes based on whether the individual has hyperkeratosis on the palms and soles (PS) or no involvement of the palms and soles (NPS). There is typically no involvement of the nails, hair, or mucosal surfaces.4
IPCRR Data for KRT1
Nine individuals fully enrolled in the International Pachyonychia Congenita Research Registry (IPCRR) were found to carry a mutation in KRT1 gene. Below is select data from the registry.
| Palmar Keratoderma | 67% |
|---|---|
| Always (never goes away) | 50% |
| Sometimes (clears up at times) | 0% |
| Seldom (hands usually clear) | 17% |
| Toenail Dystrophy | 17% |
|---|---|
| all 10 toenails thickened | 0% |
| 7-9 toenails thickened | 0% |
| 4-6 toenails thickened | 0% |
| 1-3 toenails thickened | 17% |
| Toenails – Onset | |
|---|---|
| Birth or less than 1 year | 0% |
| 1 to 4 years old | 0% |
| 5 to 14 years old | 0% |
| 15 years and over | 17% |
| Fingernail Dystrophy | 0% |
|---|---|
| all 10 toenails thickened | 0% |
| 7-9 toenails thickened | 0% |
| 4-6 toenails thickened | 0% |
| 1-3 toenails thickened | 0% |
| Oral Leukokeratosis | 0% |
|---|---|
| Cysts | 0% |
| Follicular Hyperkeratosis | 0% |
| Natal or Prenatal Teeth | 0% |
Data from 2022 Sample Size N=6
References
- Calì F, Failla P, Vinci M, Siragusa M, Schepis C. A de novo mutation of KRT1 in a baby girl causing epidermolytic ichthyosis with impressive epidermolytic palmoplantar keratoderma. Dermatol Online J. 2020;26(7):13030/qt6642w2p4. Published 2020 Jul 15.
- Virtanen, M., Vahlquist, A., Smith, S. K., Gedde-Dahl Jr, T., & Bowden, P. E. (2003). Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: unusual phenotypic alterations in Scandinavian patients with epidermolytic hyperkeratosis. Journal of investigative dermatology, 121(5), 1013-1020.
- ByGUM, A., VIrTANEN, M., BrANDruP, F., Ganemo, A., SOMMErluND, M., STrAuSS, G., & VAHlquIST, A. (2013). Generalized and naevoid epidermolytic ichthyosis in Denmark: clinical and mutational findings. Acta Dermato-Venereologica, 93(3), 309-313.
- Putra PB, Radiono S, Danarti R. Generalized epidermolytic ichthyosis with palmoplantar hyperkeratosis. Dermatol Online J. 2021;27(2):13030/qt2r24j2nm. Published 2021 Feb 15.
Above photos are from individuals in the IPCRR with confirmed KRT1 mutations.
