3. Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé Syndrome

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Synonym: fibrofolliculomas with trichodiscomas and acrochordons

Birt-Hogg-Dubé syndrome is named after the three authors of a paper that described family members with papular skin lesions on their face, forehead, scalp and neck.[1]

When these lesions were examined, the following were found:[2]

  • Fibrofolliculomas (benign tumours of the hair follicle).
  • Trichodiscomas (hamartomatous tumours of the hair disc).
  • Acrochordons ('wart with a thin neck' skin tags).

This triad of features became known as Birt-Hogg-Dubé syndrome. It is now thought that these may all just be part of the spectrum of fibrofolliculomas.[3]

  • Birt-Hogg-Dubé syndrome is a rare inherited genodermatosis.[2]
  • The condition is caused by mutation in the gene encoding folliculin which may have a role as a tumour suppressor gene.
  • The mutation is at gene map locus 17p11.2.
  • An autosomal dominant inheritance pattern has been identified.[4]
  • The actual incidence is unknown, but it is likely to be underdiagnosed.[5]
  • Onset tends to be in adulthood with skin lesions:[2]
    • These develop in the 20s or 30s and remain throughout life.
    • They are typically small, dome-shaped, papular skin lesions, about 2 mm to 4 mm in diameter, that develop over the scalp, face, neck and upper trunk. They may also be seen in the mouth.
    • They cause no symptoms and the reason for presentation is usually cosmetic.
    • Acrochordons are warty-like skin tags that may be found on the eyelids, neck, axilla and upper half of the trunk.[3]
  • Presentation may also be with renal carcinoma, spontaneous pneumothorax or another associated condition - see below.

There are a number of conditions associated with Birt-Hogg-Dubé syndrome including:[3]

  • Renal carcinomas (may be multifocal or bilateral; most commonly chromophobe renal carcinoma and oncocytic hybrid tumours).[6]
  • Pulmonary cysts.
  • Spontaneous pneumothorax.
  • Connective tissue naevi.
  • Parathyroid adenomas.
  • Flecked chorioretinopathy.
  • Bullous emphysema.
  • Lipomas and angiolipomas.
  • Parotid oncocytomas.
  • Multiple oral mucosal papules.
  • Neural tissue tumours.
  • Multiple facial angiofibromas.

Other possible associations include:

Birt-Hogg-Dubé syndrome should be looked for in any patient with multiple bilateral kidney tumours, especially if the predominant histological type is chromophobe renal cell carcinoma or hybrid oncocytic tumour.[7]
  • Skin biopsy will confirm the nature of the lesions.
  • Molecular genetic testing is available.
  • CXR (may show pulmonary cysts, bullous emphysema or pneumothorax).
  • Renal ultrasound and CT scan of the abdomen/pelvis should be performed to screen for renal tumours. Relatives should also be screened for renal cancer.
  • Consider colonoscopy because of the possible association with colonic polyps/carcinoma, although this is debated.[8][9]
  • There is no specific therapy.
  • Skin lesions may be treated by surgical removal. Dermabrasion, electrodesiccation and laser treatment have been used but the lesions may recur.[3]
  • There should be long-term follow-up for malignant change, especially renal carcinoma and possibly colonic carcinoma.
  • Monitoring and screening for associated chest conditions should be carried out.
  • Associated conditions should be managed appropriately.
  • Genetic counselling should be offered.
  • This depends on the development of associated conditions, especially renal carcinoma.
  • The tendency for associated malignancy seems variable between families.
  • Specific mutations in the folliculin gene may predispose to cancer development in Birt-Hogg-Dubé syndrome.[10]
  • Malignancy is not an invariable part of the disease.
  • Encourage patients to stop smoking because of the additive risk factor for lung disease and renal carcinoma.
  • Avoidance of high ambient pressures may reduce the risk of spontaneous pneumothorax.[11]
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Further reading & references

  1. Birt AR, Hogg GR, Dubé WJ; Birt AR, Hogg GR, Dubé WJ; Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977 Dec;113(12):1674-7.
  2. Birt-Hogg-Dube Syndrome, Online Mendelian Inheritance in Man (OMIM)
  3. Buckley KK et al; Birt-Hogg-Dube Syndrome, Medscape, May 2009
  4. Toro JR, Wei MH, Glenn GM, et al; BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube J Med Genet. 2008 Jun;45(6):321-31. Epub 2008 Jan 30.
  5. Kim EH, Jeong SY, Kim HJ, et al; A case of Birt-Hogg-Dubé syndrome. J Korean Med Sci. 2008 Apr;23(2):332-5.
  6. Schmidt LS; Birt-Hogg-Dubé syndrome, a genodermatosis that increases risk for renal carcinoma. Curr Mol Med. 2004 Dec;4(8):877-85.
  7. Adley BP, Smith ND, Nayar R, et al; Birt-Hogg-Dubé syndrome: clinicopathologic findings and genetic alterations. Arch Pathol Lab Med. 2006 Dec;130(12):1865-70.
  8. Zbar B, Alvord WG, Glenn G, et al; Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):393-400.
  9. Le Guyadec T, Dufau JP, Poulain JF, et al; Multiple trichodiscomas associated with colonic polyposis. Ann Dermatol Venereol. 1998 Oct;125(10):717-9.
  10. Palmirotta R, Donati P, Savonarola A, et al; Birt-Hogg-Dubé (BHD) syndrome: report of two novel germline mutations in the folliculin (FLCN) gene. Eur J Dermatol. 2008 Jul-Aug;18(4):382-6. Epub 2008 Jun 23.
  11. Toro JR; Birt-Hogg-Dubé Syndrome, Gene Reviews, September 2008
Original Author: Dr Huw Thomas, Dr Michelle Wright Current Version:
Last Checked: 03/06/2011 Document ID: 1865  Version: 25 © EMIS

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