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Genetics Home Reference: your guide to understanding genetic conditions
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Birt-Hogg-Dubé syndrome

Reviewed January 2013

What is Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals.

Birt-Hogg-Dubé syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dubé syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dubé syndrome.

How common is Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome is rare; its exact incidence is unknown. This condition has been reported in more than 400 families.

What genes are related to Birt-Hogg-Dubé syndrome?

Mutations in the FLCN gene cause Birt-Hogg-Dubé syndrome. This gene provides instructions for making a protein called folliculin. The normal function of this protein is unknown, but researchers believe that it may act as a tumor suppressor. Tumor suppressors prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to uncontrolled cell growth and the formation of noncancerous and cancerous tumors. Researchers have not determined how FLCN mutations increase the risk of lung problems, such as pneumothorax.

Related Gene(s)

Changes in this gene are associated with Birt-Hogg-Dubé syndrome.

  • FLCN

How do people inherit Birt-Hogg-Dubé syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered FLCN gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Less commonly, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family.

Having a single mutated copy of the FLCN gene in each cell is enough to cause the skin tumors and lung problems associated with Birt-Hogg-Dubé syndrome. However, both copies of the FLCN gene are often mutated in the kidney tumors that occur with this condition. One of the mutations is inherited from a parent, while the other occurs by chance in a kidney cell during a person's lifetime. These genetic changes disable both copies of the FLCN gene, which allows kidney cells to divide uncontrollably and form tumors.

Where can I find information about diagnosis or management of Birt-Hogg-Dubé syndrome?

These resources address the diagnosis or management of Birt-Hogg-Dubé syndrome and may include treatment providers.

  • BHD Foundation: Diagnosis/Treatment (http://www.bhdsyndrome.org/for-families/diagnosistreatment/)
  • Gene Review: Birt-Hogg-Dube Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1522/)
  • Genetic Testing Registry: Multiple fibrofolliculomas (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0346010)
  • MedlinePlus Encyclopedia: Collapsed Lung (http://www.nlm.nih.gov/medlineplus/ency/article/000087.htm)

You might also find information on the diagnosis or management of Birt-Hogg-Dubé syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/birt-hogg-dube-syndrome/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 Birt-Hogg-Dubé syndrome?

You may find the following resources about Birt-Hogg-Dubé syndrome 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 Birt-Hogg-Dubé syndrome?

  • BHD
  • fibrofolliculomas with trichodiscomas and acrochordons
  • Hornstein-Birt-Hogg-Dubé syndrome
  • Hornstein-Knickenberg syndrome

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 Birt-Hogg-Dubé syndrome?

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

What glossary definitions help with understanding Birt-Hogg-Dubé syndrome?

autosomal ; autosomal dominant ; benign ; cancer ; cell ; cysts ; gene ; incidence ; kidney ; mutation ; new mutation ; pneumothorax ; protein ; syndrome ; tumor

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

References

  • Gene Review: Birt-Hogg-Dube Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1522/)
  • Happle R. Hornstein-Birt-Hogg-Dubé syndrome: a renaming and reconsideration. Am J Med Genet A. 2012 Jun;158A(6):1247-51. doi: 10.1002/ajmg.a.35330. Epub 2012 May 11. (http://www.ncbi.nlm.nih.gov/pubmed/22581760?dopt=Abstract)
  • Khoo SK, Giraud S, Kahnoski K, Chen J, Motorna O, Nickolov R, Binet O, Lambert D, Friedel J, Lévy R, Ferlicot S, Wolkenstein P, Hammel P, Bergerheim U, Hedblad MA, Bradley M, Teh BT, Nordenskjöld M, Richard S. Clinical and genetic studies of Birt-Hogg-Dubé syndrome. J Med Genet. 2002 Dec;39(12):906-12. Erratum in: J Med Genet. 2003 Feb;40(2):150.. (http://www.ncbi.nlm.nih.gov/pubmed/12471204?dopt=Abstract)
  • Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2002 Aug;2(2):157-64. (http://www.ncbi.nlm.nih.gov/pubmed/12204536?dopt=Abstract)
  • Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002 Dec;26(12):1542-52. (http://www.ncbi.nlm.nih.gov/pubmed/12459621?dopt=Abstract)
  • Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. Am J Hum Genet. 2005 Jun;76(6):1023-33. Epub 2005 Apr 25. (http://www.ncbi.nlm.nih.gov/pubmed/15852235?dopt=Abstract)
  • Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, Turner ML, Duray P, Merino M, Hewitt S, Pavlovich CP, Glenn G, Greenberg CR, Linehan WM, Zbar B. Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001 Oct;69(4):876-82. Epub 2001 Aug 30. (http://www.ncbi.nlm.nih.gov/pubmed/11533913?dopt=Abstract)
  • Warren MB, Torres-Cabala CA, Turner ML, Merino MJ, Matrosova VY, Nickerson ML, Ma W, Linehan WM, Zbar B, Schmidt LS. Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues. Mod Pathol. 2004 Aug;17(8):998-1011. (http://www.ncbi.nlm.nih.gov/pubmed/15143337?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: January 2013
Published: April 21, 2014