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Genetics Home Reference: your guide to understanding genetic conditions
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Hereditary angioedema

Reviewed April 2009

What is hereditary angioedema?

Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.

Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.

There are three types of hereditary angioedema, called types I, II, and III, which can be distinguished by their underlying causes and levels of a protein called C1 inhibitor in the blood. The different types have similar signs and symptoms. Type III was originally thought to occur only in women, but families with affected males have been identified.

How common is hereditary angioedema?

Hereditary angioedema is estimated to affect 1 in 50,000 people. Type I is the most common, accounting for 85 percent of cases. Type II occurs in 15 percent of cases, and type III is very rare.

What genes are related to hereditary angioedema?

Mutations in the SERPING1 gene cause hereditary angioedema type I and type II. The SERPING1 gene provides instructions for making the C1 inhibitor protein, which is important for controlling inflammation. C1 inhibitor blocks the activity of certain proteins that promote inflammation. Mutations that cause hereditary angioedema type I lead to reduced levels of C1 inhibitor in the blood, while mutations that cause type II result in the production of a C1 inhibitor that functions abnormally. Without the proper levels of functional C1 inhibitor, excessive amounts of a protein fragment (peptide) called bradykinin are generated. Bradykinin promotes inflammation by increasing the leakage of fluid through the walls of blood vessels into body tissues. Excessive accumulation of fluids in body tissues causes the episodes of swelling seen in individuals with hereditary angioedema type I and type II.

Mutations in the F12 gene are associated with some cases of hereditary angioedema type III. This gene provides instructions for making a protein called coagulation factor XII. In addition to playing a critical role in blood clotting (coagulation), factor XII is also an important stimulator of inflammation and is involved in the production of bradykinin. Certain mutations in the F12 gene result in the production of factor XII with increased activity. As a result, more bradykinin is generated and blood vessel walls become more leaky, which leads to episodes of swelling in people with hereditary angioedema type III.

The cause of other cases of hereditary angioedema type III remains unknown. Mutations in one or more as-yet unidentified genes may be responsible for the disorder in these cases.

Related Gene(s)

Changes in these genes are associated with hereditary angioedema.

  • F12
  • SERPING1

How do people inherit hereditary angioedema?

This 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.

In some cases, an affected person inherits the mutation from one affected parent. Other 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 hereditary angioedema?

These resources address the diagnosis or management of hereditary angioedema and may include treatment providers.

  • Genetic Testing Registry: Hereditary angioneurotic edema (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0019243)
  • Genetic Testing Registry: Hereditary angioneurotic edema with normal C1 esterase inhibitor activity (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857728)
  • Genetic Testing Registry: Hereditary C1 esterase inhibitor deficiency - dysfunctional factor (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1862892)
  • MedlinePlus Encyclopedia: Hereditary angioedema (http://www.nlm.nih.gov/medlineplus/ency/article/001456.htm)

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

You may find the following resources about hereditary angioedema 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 hereditary angioedema?

  • C1 esterase inhibitor deficiency
  • C1 inhibitor deficiency
  • HAE
  • HANE
  • hereditary angioneurotic edema

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 hereditary angioedema?

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

What glossary definitions help with understanding hereditary angioedema?

autosomal ; autosomal dominant ; blood clotting ; bradykinin ; cell ; clotting ; coagulation ; deficiency ; edema ; erythema ; gene ; hereditary ; inflammation ; inherited ; mutation ; obstruction ; peptide ; protein ; puberty ; stress ; 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

  • OMIM: ANGIOEDEMA, HEREDITARY, TYPE I (http://omim.org/entry/106100)
  • OMIM: ANGIOEDEMA, HEREDITARY, TYPE III (http://omim.org/entry/610618)
  • Cichon S, Martin L, Hennies HC, Müller F, Van Driessche K, Karpushova A, Stevens W, Colombo R, Renné T, Drouet C, Bork K, Nöthen MM. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet. 2006 Dec;79(6):1098-104. Epub 2006 Oct 18. (http://www.ncbi.nlm.nih.gov/pubmed/17186468?dopt=Abstract)
  • Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009 Feb;15(2):69-78. doi: 10.1016/j.molmed.2008.12.001. Epub 2009 Jan 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19162547?dopt=Abstract)
  • Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006 May 19;343(4):1286-9. (http://www.ncbi.nlm.nih.gov/pubmed/16638441?dopt=Abstract)
  • Gösswein T, Kocot A, Emmert G, Kreuz W, Martinez-Saguer I, Aygören-Pürsün E, Rusicke E, Bork K, Oldenburg J, Müller CR. Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet Genome Res. 2008;121(3-4):181-8. doi: 10.1159/000138883. Epub 2008 Aug 28. (http://www.ncbi.nlm.nih.gov/pubmed/18758157?dopt=Abstract)
  • Krishnamurthy A, Naguwa SM, Gershwin ME. Pediatric angioedema. Clin Rev Allergy Immunol. 2008 Apr;34(2):250-9. doi: 10.1007/s12016-007-8037-y. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18330729?dopt=Abstract)
  • Martin L, Raison-Peyron N, Nöthen MM, Cichon S, Drouet C. Hereditary angioedema with normal C1 inhibitor gene in a family with affected women and men is associated with the p.Thr328Lys mutation in the F12 gene. J Allergy Clin Immunol. 2007 Oct;120(4):975-7. Epub 2007 Sep 7. (http://www.ncbi.nlm.nih.gov/pubmed/17825897?dopt=Abstract)
  • Pappalardo E, Caccia S, Suffritti C, Tordai A, Zingale LC, Cicardi M. Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol. 2008 Aug;45(13):3536-44. doi: 10.1016/j.molimm.2008.05.007. Epub 2008 Jun 30. (http://www.ncbi.nlm.nih.gov/pubmed/18586324?dopt=Abstract)
  • Wouters D, Wagenaar-Bos I, van Ham M, Zeerleder S. C1 inhibitor: just a serine protease inhibitor? New and old considerations on therapeutic applications of C1 inhibitor. Expert Opin Biol Ther. 2008 Aug;8(8):1225-40. doi: 10.1517/14712598.8.8.1225 . Review. (http://www.ncbi.nlm.nih.gov/pubmed/18613773?dopt=Abstract)
  • Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18768946?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: April 2009
Published: September 15, 2014