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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Junctional epidermolysis bullosa

Reviewed September 2009

What is junctional epidermolysis bullosa?

Junctional epidermolysis bullosa (JEB) is one of the major forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types: Herlitz JEB and non-Herlitz JEB. Although the types differ in severity, their features overlap significantly, and they can be caused by mutations in the same genes.

Herlitz JEB is the more severe form of the condition. From birth or early infancy, affected individuals have blistering over large regions of the body. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. As a result, many affected children have chronic malnutrition and slow growth. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a buildup of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing.

Other complications of Herlitz JEB can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement, and hair loss (alopecia). Because the signs and symptoms of Herlitz JEB are so severe, infants with this condition usually do not survive beyond the first year of life.

The milder form of junctional epidermolysis bullosa is called non-Herlitz JEB. The blistering associated with non-Herlitz JEB may be limited to the hands, feet, knees, and elbows, and it often improves after the newborn period. Other characteristic features of this condition include alopecia, malformed fingernails and toenails, and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. Non-Herlitz JEB is typically associated with a normal lifespan.

How common is junctional epidermolysis bullosa?

Both types of junctional epidermolysis bullosa are rare, affecting fewer than 1 per million people in the United States.

What genes are related to junctional epidermolysis bullosa?

Junctional epidermolysis bullosa results from mutations in the LAMA3, LAMB3, LAMC2, and COL17A1 genes. Mutations in each of these genes can cause Herlitz JEB or non-Herlitz JEB. LAMB3 gene mutations are the most common, causing about 70 percent of all cases of junctional epidermolysis bullosa.

The LAMA3, LAMB3, and LAMC2 genes each provide instructions for making one part (subunit) of a protein called laminin 332. This protein plays an important role in strengthening and stabilizing the skin by helping to attach the top layer of skin (the epidermis) to underlying layers. Mutations in any of the three laminin 332 genes lead to the production of a defective or nonfunctional version of this protein. Without functional laminin 332, cells in the epidermis are fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the formation of blisters.

The COL17A1 gene provides instructions for making a protein that is used to assemble type XVII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type XVII collagen helps attach the epidermis to underlying layers of skin, making the skin strong and flexible. Mutations in the COL17A1 gene prevent the normal formation of collagen XVII. As a result, the skin is less resistant to friction and minor trauma and blisters easily. Most COL17A1 gene mutations cause non-Herlitz JEB, although a few individuals with mutations in this gene have had the more severe Herlitz JEB.

Related Gene(s)

Changes in these genes are associated with junctional epidermolysis bullosa.

  • COL17A1
  • LAMA3
  • LAMB3
  • LAMC2

How do people inherit junctional epidermolysis bullosa?

Both types of junctional epidermolysis bullosa are 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 junctional epidermolysis bullosa?

These resources address the diagnosis or management of junctional epidermolysis bullosa and may include treatment providers.

  • Epidermolysis Bullosa Center, Cincinnati Children's Hospital Medical Center (
  • Gene Review: Junctional Epidermolysis Bullosa (
  • Genetic Testing Registry: Adult junctional epidermolysis bullosa (
  • Genetic Testing Registry: Epidermolysis bullosa, junctional (
  • Genetic Testing Registry: Junctional epidermolysis bullosa gravis of Herlitz (
  • MedlinePlus Encyclopedia: Epidermolysis Bullosa (

You might also find information on the diagnosis or management of junctional epidermolysis bullosa in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about junctional epidermolysis bullosa?

You may find the following resources about junctional epidermolysis bullosa 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 junctional epidermolysis bullosa?

  • Epidermolysis Bullosa, Junctional
  • JEB

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about junctional epidermolysis bullosa?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding junctional epidermolysis bullosa?

alopecia ; autosomal ; autosomal recessive ; benign ; blister ; cell ; chronic ; collagen ; digestive ; enamel ; epidermis ; gene ; inherited ; injury ; joint ; mucous ; protein ; recessive ; subunit ; tissue ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Castori M, Floriddia G, De Luca N, Pascucci M, Ghirri P, Boccaletti V, El Hachem M, Zambruno G, Castiglia D. Herlitz junctional epidermolysis bullosa: laminin-5 mutational profile and carrier frequency in the Italian population. Br J Dermatol. 2008 Jan;158(1):38-44. Epub 2007 Oct 4. (
  • Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, McGrath JA, Mellerio JE, Murrell DF, Shimizu H, Uitto J, Vahlquist A, Woodley D, Zambruno G. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. 2008 Jun;58(6):931-50. doi: 10.1016/j.jaad.2008.02.004. Epub 2008 Apr 18. (
  • Gene Review: Junctional Epidermolysis Bullosa (
  • Mühle C, Jiang QJ, Charlesworth A, Bruckner-Tuderman L, Meneguzzi G, Schneider H. Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease. Hum Genet. 2005 Jan;116(1-2):33-42. Epub 2004 Nov 5. (
  • Nakano A, Lestringant GG, Paperna T, Bergman R, Gershoni R, Frossard P, Kanaan M, Meneguzzi G, Richard G, Pfendner E, Uitto J, Pulkkinen L, Sprecher E. Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families. J Am Acad Dermatol. 2002 Apr;46(4):510-6. (
  • Pfendner EG, Bruckner A, Conget P, Mellerio J, Palisson F, Lucky AW. Basic science of epidermolysis bullosa and diagnostic and molecular characterization: Proceedings of the IInd International Symposium on Epidermolysis Bullosa, Santiago, Chile, 2005. Int J Dermatol. 2007 Aug;46(8):781-94. (
  • Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol. 1999 Feb;18(1):29-42. Review. (
  • Varki R, Sadowski S, Pfendner E, Uitto J. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. J Med Genet. 2006 Aug;43(8):641-52. Epub 2006 Feb 10. (


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? ( in the Handbook.

Reviewed: September 2009
Published: February 8, 2016