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Genetics Home Reference: your guide to understanding genetic conditions
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Epidermolytic hyperkeratosis

Reviewed November 2011

What is epidermolytic hyperkeratosis?

Epidermolytic hyperkeratosis is a skin disorder that is present at birth. Affected babies may have very red skin (erythroderma) and severe blisters. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis).

As affected individuals get older, blistering is less frequent, erythroderma becomes less evident, and the skin becomes thick (hyperkeratotic), especially over joints, on areas of skin that come into contact with each other, or on the scalp or neck. This thickened skin is usually darker than normal. Bacteria can grow in the thick skin, often causing a distinct odor.

Epidermolytic hyperkeratosis can be categorized into two types. People with PS-type epidermolytic hyperkeratosis have thick skin on the palms of their hands and soles of their feet (palmoplantar or palm/sole hyperkeratosis) in addition to other areas of the body. People with the other type, NPS-type, do not have extensive palmoplantar hyperkeratosis but do have hyperkeratosis on other areas of the body.

Epidermolytic hyperkeratosis is part of a group of conditions called ichthyoses, which refers to the scaly skin seen in individuals with related disorders. However, in epidermolytic hyperkeratosis, the skin is thick but not scaly as in some of the other conditions in the group.

How common is epidermolytic hyperkeratosis?

Epidermolytic hyperkeratosis affects approximately 1 in 200,000 to 300,000 people worldwide.

What genes are related to epidermolytic hyperkeratosis?

Mutations in the KRT1 or KRT10 genes are responsible for epidermolytic hyperkeratosis. These genes provide instructions for making proteins called keratin 1 and keratin 10, which are found in cells called keratinocytes in the outer layer of the skin (the epidermis). The tough, fibrous keratin proteins attach to each other and form fibers called intermediate filaments, which form networks and provide strength and resiliency to the epidermis.

Mutations in the KRT1 or KRT10 genes lead to changes in the keratin proteins, preventing them from forming strong, stable intermediate filament networks within cells. Without a strong network, keratinocytes become fragile and are easily damaged, which can lead to blistering in response to friction or mild trauma. It is unclear how these mutations cause the overgrowth of epidermal cells that results in hyperkeratotic skin.

KRT1 gene mutations are associated with PS-type epidermal hyperkeratosis, and KRT10 gene mutations are usually associated with NPS-type. The keratin 1 protein is present in the keratinocytes of the skin on the palms of the hands and the soles of the feet as well as other parts of the body, so mutations in the KRT1 gene lead to skin problems in these areas. The keratin 10 protein is not found in the skin of the palms and soles, so these areas are unaffected by mutations in the KRT10 gene.

Related Gene(s)

Changes in these genes are associated with epidermolytic hyperkeratosis.

  • KRT1
  • KRT10

How do people inherit epidermolytic hyperkeratosis?

Epidermolytic hyperkeratosis can have different inheritance patterns. About half of the cases of this condition result from new mutations in the KRT1 or KRT10 gene and occur in people with no history of the disorder in their family.

When epidermolytic hyperkeratosis is inherited, it is usually in an autosomal dominant pattern, which means one copy of the altered KRT1 or KRT10 gene in each cell is sufficient to cause the disorder.

Very rarely, epidermolytic hyperkeratosis caused by mutations in the KRT10 gene can be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of epidermolytic hyperkeratosis?

These resources address the diagnosis or management of epidermolytic hyperkeratosis and may include treatment providers.

  • Genetic Testing Registry: Bullous ichthyosiform erythroderma (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0079153)
  • The Swedish Information Centre for Rare Diseases: Ichthyosis (http://www.socialstyrelsen.se/rarediseases/ichthyosis)

You might also find information on the diagnosis or management of epidermolytic hyperkeratosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/epidermolytic-hyperkeratosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about epidermolytic hyperkeratosis?

You may find the following resources about epidermolytic hyperkeratosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for epidermolytic hyperkeratosis?

  • BCIE
  • BIE
  • bullous congenital ichthyosiform erythroderma
  • bullous erythroderma ichthyosiforme
  • bullous erythroderma ichthyosiformis congenita of Brocq
  • bullous ichthyosiform erythroderma
  • EHK
  • epidermolytic ichthyosis
  • hyperkeratosis, epidermolytic

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about epidermolytic hyperkeratosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding epidermolytic hyperkeratosis?

autosomal ; autosomal dominant ; autosomal recessive ; bacteria ; cell ; congenital ; epidermis ; erythroderma ; gene ; ichthyosiform ; ichthyosis ; inheritance ; intermediate filaments ; keratin ; protein ; recessive ; sepsis ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Arch Biochem Biophys. 2011 Apr 15;508(2):123-37. doi: 10.1016/j.abb.2010.12.019. Epub 2010 Dec 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21176769?dopt=Abstract)
  • Chipev CC, Korge BP, Markova N, Bale SJ, DiGiovanna JJ, Compton JG, Steinert PM. A leucine----proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis. Cell. 1992 Sep 4;70(5):821-8. (http://www.ncbi.nlm.nih.gov/pubmed/1381288?dopt=Abstract)
  • DiGiovanna JJ, Bale SJ. Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol. 1994 Aug;130(8):1026-35. (http://www.ncbi.nlm.nih.gov/pubmed/8053700?dopt=Abstract)
  • Yang JM, Chipev CC, DiGiovanna JJ, Bale SJ, Marekov LN, Steinert PM, Compton JG. Mutations in the H1 and 1A domains in the keratin 1 gene in epidermolytic hyperkeratosis. J Invest Dermatol. 1994 Jan;102(1):17-23. (http://www.ncbi.nlm.nih.gov/pubmed/7507151?dopt=Abstract)
  • Yang JM, Nam K, Kim HC, Lee JH, Park JK, Wu K, Lee ES, Steinert PM. A novel glutamic acid to aspartic acid mutation near the end of the 2B rod domain in the keratin 1 chain in epidermolytic hyperkeratosis. J Invest Dermatol. 1999 Mar;112(3):376-9. (http://www.ncbi.nlm.nih.gov/pubmed/10084317?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2011
Published: April 21, 2014