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

Genetics

• 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

Epidemiology

• The actual incidence is unknown, but it is likely to be underdiagnosed.⁵

Presentation

• 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.

Associations

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:

• Colonic polyps and colonic adenocarcinoma.
• Medullary thyroid carcinoma.

Investigations

• 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

Management

• 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.

Prognosis

• 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.

Prevention

• 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

Document references

1. Birt AR, Hogg GR, Dubé WJ; Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977 Dec;113(12):1674-7. [abstract]
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. [abstract]
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. [abstract]
6. Schmidt LS; Birt-Hogg-Dubé syndrome, a genodermatosis that increases risk for renal carcinoma. Curr Mol Med. 2004 Dec;4(8):877-85. [abstract]
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. [abstract]
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. [abstract]
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. [abstract]
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. [abstract]
11. Toro JR; Birt-Hogg-Dubé Syndrome, Gene Reviews, September 2008

Internet and further reading

• Birt-Hogg-Dube syndrome, DermNet NZ, Accessed December 2008; Shows pictures of skin lesions
• Kluger N, Giraud S, Coupier I, et al; Birt-Hogg-Dube syndrome: clinical and genetic studies of 10 French families. Br J Dermatol. 2010 Mar;162(3):527-37. Epub 2009 Sep 26. [abstract]

Acknowledgements