Commonly referred to as Epidermolytic Palmoplantar Keratoderma (EPPK) or Vorner Disease
Facts
- What does KRT9 stand for? Keratin 9.
- What does the KRT9 gene do? Encodes keratin 9.1
- What happens when KRT9 becomes mutated? Structural integrity to epithelial cells is compromised.2
- Clinical significance of mutation? Hyperkeratosis of the palms and soles.1
About K9-pEDD or Epidermolytic Palmoplantar Keratoderma (EPPK)
Skin disease caused by KRT9 mutations is known as Epidermolytic Palmoplantar Keratoderma (EPPK).1 However, not all cases of EPPK are caused by KRT9 mutations, as some can be attributed to mutations in KRT 1.2 The disease is very rare and is estimated to have a prevalence of 1.0 to 4.4 per 100,000.3 EPPK is passed down from a parent to their offspring in an autosomal dominant inheritance pattern.1,2,3 This means that it only takes one copy of the mutated KRT9 gene from one parent to cause EPPK. The parent who has EPPK has a 50% chance of passing the mutated KRT9 gene in each pregnancy. Genetic testing is necessary to determine whether symptoms of EPPK are caused by a mutation in the KRT9 gene.2
Symptoms of KRT9
Signs of EPPK appear around three to twelve months of age as skin redness of the palms and soles. Typically after a child is one year old, yellow-brown, diffuse hyperkeratosis appears on the surface.2 Several small hyperkeratotic lesions start to appear on the palms of the hands as well as the soles of the feet. Hyperkeratotic lesions are defined papules that appear as thickening of the outer layer of skin. The skin has low resistance to trauma.1 Therefore, cracks, blisters, and erosions may appear in areas of the surface that are subject to mechanical force.1,2 The degree of hyperkeratosis can vary from one family to another as well as among members from the same family.2 Other signs and symptoms of EPPK may include increased sweating, curved fingers, knuckle pads on the digital joints, and decreased sensitivity to heat.1,3
IPCRR Data for KRT9
Nine individuals fully enrolled in the International Pachyonychia Congenita Research Registry (IPCRR) were found not to have PC but instead carry a mutation in KRT9 gene. Three are in the United Kingdom and three are in the United States. The other individuals are from Australia, France, and Vietnam. Four are female, four are males, and one did not disclose. Below is select data from the registry.
| Plantar Keratoderma | 78% |
|---|---|
| Always (never goes away) | 78% |
| Sometimes (clears up at times) | 0% |
| Seldom (feet usually clear) | 0% |
| Plantar Keratoderma – Onset | |
|---|---|
| Birth or less than 1 year | 57% |
| 1 to 4 years old | 29% |
| 5 to 14 years old | 14% |
| 15 years and over | 0% |
| Plantar Pain | 67% |
|---|---|
| Often require medications for pain | 11% |
| Very painful, but do not use medications | 22% |
| Somewhat painful | 34% |
| Palmar Keratoderma | 78% |
|---|---|
| Always (never goes away) | 78% |
| Sometimes (clears up at times) | 0% |
| Seldom (hands usually clear) | 0% |
| Toenail Dystrophy | 55% |
|---|---|
| all 10 toenails thickened | 0% |
| 7-9 toenails thickened | 0% |
| 4-6 toenails thickened | 22% |
| 1-3 toenails thickened | 33% |
| Toenails – Onset | |
|---|---|
| Birth or less than 1 year | 0% |
| 1 to 4 years old | 40% |
| 5 to 14 years old | 40% |
| 15 years and over | 20% |
| Fingernail Dystrophy | 22% |
|---|---|
| all 10 toenails thickened | 0% |
| 7-9 toenails thickened | 0% |
| 4-6 toenails thickened | 11% |
| 1-3 toenails thickened | 11% |
| Fingernails – Onset | |
|---|---|
| Birth or less than 1 year | 0% |
| 1 to 4 years old | 50% |
| 5 to 14 years old | 50% |
| 15 years and over | 0% |
| Oral Leukokeratosis | 11% |
|---|---|
| Cysts | 0% |
| Follicular Hyperkeratosis | 0% |
| Natal or Prenatal Teeth | 0% |
Data from 2022 Sample Size N=9
References
- Lopez‐Valdez, J., Rivera‐Vega, M. R., Gonzalez‐Huerta, L. M., Cazarin, J., & Cuevas‐Covarrubias, S. (2013). Analysis of the KRT 9 Gene in a Mexican Family with Epidermolytic Palmoplantar Keratoderma. Pediatric Dermatology, 30(3), 354-358.
- Ke, H. P., Jiang, H. L., Lv, Y. S., Huang, Y. Z., Liu, R. R., Chen, X. L., … & Zhang, X. N. (2014). KRT9 gene mutation as a reliable indicator in the prenatal molecular diagnosis of epidermolytic palmoplantar keratoderma. Gene, 546(1), 124-128.
- Xiao, H., Guo, Y., Yi, J., Xia, H., Xu, H., Yuan, L., … & Deng, H. (2018). Identification of a novel keratin 9 missense mutation in a Chinese family with epidermolytic palmoplantar keratoderma. Cellular Physiology and Biochemistry, 46(5), 1919-1929.
Above photos are from individuals in the IPCRR with confirmed KRT9 mutations.
