Birt-Hogg-Dubé syndrome (also known as BHD) is an inherited condition named after the three Canadian doctors that described it in 1977 – Arthur R. Birt, Georgina R. Hogg, and William J. Dubé (1).
The first reference to any of the symptoms now associated with BHD was actually in 1925. Burnier and Rejsek described a female with several small, flesh-coloured bumps on the face, neck and chest (2). They took samples of these lesions and found that they always developed around hair follicles. They termed these skin bumps perifollicular fibromas. Many similar reports followed, including one in 1975 from Hornstein and Knickenberg (3). They reported 2 siblings with the previously described skin lesions. . Their father had similar skin lesions as well as kidney and lung cysts.
In 1977, Birt and colleagues described a family with a history of thyroid cancer and skin lesions (1). They described the inherited nature of the skin lesions and termed them fibrofolliculomas. They also described other skin lesions called trichodiscomas and acrochordons (skin tags). This triad of skin lesions became known as Birt-Hogg-Dubé syndrome. However, it should be noted that it was later discovered that the family described by Birt and colleagues had another inherited condition called multiple endocrine neoplasia type 2 (MEN2). Although thyroid cancer has since been reported in people with BHD, MEN2 has a direct link to thyroid cancer.
At first, BHD was thought to be a skin condition. It is now known that BHD can also cause lung cysts, collapsed lungs, and kidney cancer. However, it wasn’t until 1986 when the association of collapsed lungs was made with fibrofolliculomas (4). The first case of kidney cancer in BHD was reported in 1993 (5). BHD mainly affects adults, with lung cysts, collapsed lungs and skin lesions usually appearing in a person’s 20s and 30s. Kidney cancer is thought to occur at an average age of 50.
There is no typical person with BHD. Symptoms can vary between people and can develop at different times. Some people may have no symptoms or may only develop symptoms later in life. No two people will be the same, even if they’re from the same family. At the moment there is no way of predicting who will get which symptoms or when, but roughly (6):
People with BHD can help researchers and clinicians learn more about which symptoms individuals are at risk from by registering with the BHD Syndrome International Registry (BIRT).
BHD syndrome is an inherited condition associated with mutations in the folliculin (FLCN) gene, and only a genetic test can find these mutations. Having the symptoms of BHD suggests that you might have BHD, but there are other conditions that can also cause these symptoms. Currently, there are no official diagnostic guidelines for BHD. Most people are diagnosed with BHD through genetic testing. However, a small number of people have BHD but do not have a mutation in FLCN. It is therefore also possible to be diagnosed with BHD by a clinician. They will take detailed information on your symptoms and family history to diagnose you.
BHD is a rare disease with only roughly 600 reported families worldwide, however many researchers believe it is under diagnosed (7). Because BHD is so rare, many doctors have not heard of it, so there are probably many more families with this disease that haven’t been diagnosed.
Researchers are currently investigating the function of the FLCN protein and how a mutation in this gene causes the symptoms of BHD. The ultimate aim of scientific research is to develop treatments to prevent or cure BHD.
The ‘For Families’ pages contain detailed information about BHD including the different symptoms. There are also a number of useful resources such as leaflets and a map to help you find a specialist in your area. We can also help you find a doctor or help with getting a genetic test. Contact us at contact@bhdsyndrome.org
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References
1. Birt AR, Hogg GR, Dubé WJ. Hereditary Multiple Fibrofolliculomas With Trichodiscomas and Acrochordons. Arch Dermatol [Internet]. 1977 Dec 1 [cited 2021 May 10];113(12):1674–7. Available from: https://jamanetwork.com/journals/jamadermatology/fullarticle/538004
2. Rejsek and Burnier, Fibromes sous-cutanes peripilares multiples du cou. Bull Soc francq dermat et syph, 192532: p. 242-243.
3. Hornstein O., Knickenberg M. Perifollicular Fibromatosis Cutis with Polyps of the Colon – a Cutaneo-Intestinal Syndrome sui generis. Arch Derm Res. 1975;253:161–175. [PubMed]
4. Binet O. et al. Fibromes perifolliculaires polypose colique familaile pneumothorax spontanes familiaux. Ann Dermatol Venereol. 1986;113:928–930.
5. Roth J.S. et al. Bilateral renal cell carcinoma in the Birt-Hogg-Dube syndrome. J Am Acad Dermatol. 1993;29(6):1055–6. [PubMed]
6. Schmidt LS, Linehan WM. FLCN: The causative gene for Birt-Hogg-Dubé syndrome. Vol. 640, Gene. Elsevier B.V.; 2018. p. 28–42.
7. Birt-Hogg-Dubé Syndrome – NORD (National Organization for Rare Disorders) [Internet]. [cited 2021 May 10]. Available from: https://rarediseases.org/rare-diseases/birt-hogg-dube-syndrome/
Last Updated: September 2022
Review date: September 2024