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Anhidrotic ectodermal dysplasia with immune deficiency

Reviewed August 2013

What is anhidrotic ectodermal dysplasia with immune deficiency?

Anhidrotic ectodermal dysplasia with immune deficiency (EDA-ID) is a form of ectodermal dysplasia, which is a group of conditions characterized by abnormal development of ectodermal tissues including the skin, hair, teeth, and sweat glands. In addition, immune system function is reduced in people with EDA-ID. The signs and symptoms of EDA-ID are evident soon after birth.

Skin abnormalities in people with EDA-ID include areas that are dry, wrinkled, or darker in color than the surrounding skin. Affected individuals tend to have sparse scalp and body hair (hypotrichosis). EDA-ID is also characterized by missing teeth (hypodontia) or teeth that are small and pointed. Most people with EDA-ID have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. An inability to sweat (anhidrosis) can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather.

The immune deficiency in EDA-ID varies among people with this condition. People with EDA-ID often produce abnormally low levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. A reduction in antibodies makes it difficult for people with this disorder to fight off infections. In EDA-ID, immune system cells called T cells and B cells have a decreased ability to recognize and respond to foreign invaders (such as bacteria, viruses, and yeast) that have sugar molecules attached to their surface (glycan antigens). Other key aspects of the immune system may also be impaired, leading to recurrent infections.

People with EDA-ID commonly get infections in the lungs (pneumonia), ears (otitis media), sinuses (sinusitis), lymph nodes (lymphadenitis), skin, bones, and GI tract. Approximately one quarter of individuals with EDA-ID have disorders involving abnormal inflammation, such as inflammatory bowel disease or rheumatoid arthritis.

The life expectancy of affected individuals depends of the severity of the immune deficiency; most people with this condition do not live past childhood.

There are two forms of this condition that have similar signs and symptoms and are distinguished by the modes of inheritance: X-linked recessive or autosomal dominant.

How common is anhidrotic ectodermal dysplasia with immune deficiency?

The prevalence of the X-linked recessive type of EDA-ID is estimated to be 1 in 250,000 individuals. Only a few cases of the autosomal dominant form have been described in the scientific literature.

What genes are related to anhidrotic ectodermal dysplasia with immune deficiency?

Mutations in the IKBKG gene cause X-linked recessive EDA-ID, and mutations in the NFKBIA gene cause autosomal dominant EDA-ID. The proteins produced from these two genes regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins (a protein complex) that binds to DNA and controls the activity of other genes, including genes that direct the body's immune responses and inflammatory reactions. It also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).

The IKBKG and NFKBIA gene mutations responsible for EDA-ID result in the production of proteins with impaired function, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling pathways within immune cells, resulting in immune deficiency. It is unclear how gene mutations alter the development of the skin, teeth, sweat glands, and other tissues, although it is likely caused by abnormal nuclear factor-kappa-B signaling in other types of cells.

Related Gene(s)

Changes in these genes are associated with anhidrotic ectodermal dysplasia with immune deficiency.

  • IKBKG
  • NFKBIA

How do people inherit anhidrotic ectodermal dysplasia with immune deficiency?

When EDA-ID is caused by mutations in the IKBKG gene, it is inherited in an X-linked recessive pattern. The IKBKG gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of the IKBKG gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

When EDA-ID is caused by mutations in the NFKBIA gene, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of anhidrotic ectodermal dysplasia with immune deficiency?

These resources address the diagnosis or management of anhidrotic ectodermal dysplasia with immune deficiency and may include treatment providers.

  • Genetic Testing Registry: Anhidrotic ectodermal dysplasia with immune deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1846007)
  • Genetic Testing Registry: Hypohidrotic ectodermal dysplasia with immune deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1846006)
  • MedlinePlus Encyclopedia: Immunodeficiency Disorders (http://www.nlm.nih.gov/medlineplus/ency/article/000818.htm)

You might also find information on the diagnosis or management of anhidrotic ectodermal dysplasia with immune deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency/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 anhidrotic ectodermal dysplasia with immune deficiency?

You may find the following resources about anhidrotic ectodermal dysplasia with immune deficiency 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 anhidrotic ectodermal dysplasia with immune deficiency?

  • ectodermal dysplasia, hypohidrotic, with immune deficiency
  • EDA-ID
  • HED-ID
  • hyper-IgM immunodeficiency with hypohidrotic ectodermal dysplasia
  • hypohidrotic ectodermal dysplasia with immune deficiency

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 anhidrotic ectodermal dysplasia with immune deficiency?

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

What glossary definitions help with understanding anhidrotic ectodermal dysplasia with immune deficiency?

anhidrosis ; antigens ; apoptosis ; arthritis ; autosomal ; autosomal dominant ; bacteria ; cell ; chromosome ; deficiency ; DNA ; dysplasia ; gene ; glycan ; hyperthermia ; hypodontia ; hypohidrosis ; hypotrichosis ; immune system ; immunodeficiency ; infection ; inflammation ; inheritance ; inherited ; lymph ; mutation ; otitis media ; pneumonia ; prevalence ; protein ; recessive ; sex chromosomes ; sinusitis ; X-linked recessive

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

References

  • Hubeau M, Ngadjeua F, Puel A, Israel L, Feinberg J, Chrabieh M, Belani K, Bodemer C, Fabre I, Plebani A, Boisson-Dupuis S, Picard C, Fischer A, Israel A, Abel L, Veron M, Casanova JL, Agou F, Bustamante J. New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein. Blood. 2011 Jul 28;118(4):926-35. doi: 10.1182/blood-2010-10-315234. Epub 2011 May 26. (http://www.ncbi.nlm.nih.gov/pubmed/21622647?dopt=Abstract)
  • Kawai T, Nishikomori R, Heike T. Diagnosis and treatment in anhidrotic ectodermal dysplasia with immunodeficiency. Allergol Int. 2012 Jun;61(2):207-17. doi: 10.2332/allergolint.12-RAI-0446. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22635013?dopt=Abstract)
  • Mancini AJ, Lawley LP, Uzel G. X-linked ectodermal dysplasia with immunodeficiency caused by NEMO mutation: early recognition and diagnosis. Arch Dermatol. 2008 Mar;144(3):342-6. doi: 10.1001/archderm.144.3.342. (http://www.ncbi.nlm.nih.gov/pubmed/18347290?dopt=Abstract)
  • Mooster JL, Cancrini C, Simonetti A, Rossi P, Di Matteo G, Romiti ML, Di Cesare S, Notarangelo L, Geha RS, McDonald DR. Immune deficiency caused by impaired expression of nuclear factor-kappaB essential modifier (NEMO) because of a mutation in the 5' untranslated region of the NEMO gene. J Allergy Clin Immunol. 2010 Jul;126(1):127-32.e7. doi: 10.1016/j.jaci.2010.04.026. Epub 2010 Jun 12. (http://www.ncbi.nlm.nih.gov/pubmed/20542322?dopt=Abstract)
  • Temmerman ST, Ma CA, Zhao Y, Keenan J, Aksentijevich I, Fessler M, Brown MR, Knutsen A, Shapiro R, Jain A. Defective nuclear IKKα function in patients with ectodermal dysplasia with immune deficiency. J Clin Invest. 2012 Jan 3;122(1):315-26. doi: 10.1172/JCI42534. Epub 2011 Dec 12. (http://www.ncbi.nlm.nih.gov/pubmed/22156202?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: August 2013
Published: September 22, 2014