Birt-Hogg-Dubé Syndrome

Approved by the Cancer.Net Editorial Board, 01/2020

What is Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome (BHD) is a hereditary condition associated with multiple non-cancerous (benign) skin tumors, lung cysts, and an increased risk of kidney lesions (cysts, benign tumors, and kidney cancer.) Symptoms of BHD generally do not appear until adulthood.

The most common skin tumors in BHD are called fibrofolliculomas. These are pale or flesh-colored tumors that occur in the hair follicles. Other skin tumors associated with BHD are trichodiscomas.  Researchers are looking into whether, rather than being different tumors, fibrofolliculomas and trichodiscomas may be different stages of a single process. The lung cysts in BHD are commonly at the bases of the lung and are not associated with smoking. In general, lung cysts do not cause problems with breathing and are currently not believed to increase the risk of lung cancer. However, cysts can rupture. Therefore, there is an increased risk of spontaneous pneumothorax (collapsed lung), which is air leaking out of the lungs and into the chest cavity. Many different types of kidney tumor types (histologies) have been seen in people with BHD, with the most common forms being hybrid oncocytic tumors (HOTs), chromophobe, and oncocytoma. In BHD, it is common for tumors to be on both kidneys (called bilateral) with tumors found in more than 1 place (called multifocal). When observed, these tumors tend to grow slowly, but they are likely to spread if left untreated.

What causes BHD?

BHD is a genetic condition. This means that the cancer risk and other features of BHD can be passed from generation to generation in a family. A mutation (change) in a specific gene called FLCN, which creates a protein called folliculin, is causes nearly all cases of BHD. FLCN is currently thought to be a tumor suppressor gene. A tumor suppressor gene’s natural role in the body is to make proteins that prevent tumor formation by limiting cell growth. Research is ongoing to learn more about BHD.

How is BHD inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. BHD follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 copy of the gene but that is enough to cause the condition. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. Occasionally there are de novo cases in people where the genetic change is present but it was not inherited, called an acquired mutation.

Having the mutation in 1 copy of the gene is enough to cause BHD. However, current research shows that tumors develop when there is an acquired second mutation (somatic mutation) in the normal FLCN allele (version of a specific gene). Then, with both copies of the FLCN gene altered, the cell loses its ability to suppress tumor growth leading to tumor formation.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over a decade, and more recently has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is BHD?

BHD is considered to be rare. The exact number of people and families who have BHD is unknown. However, it has been estimated that the carrier frequency is 1 per every 200,000 individuals.

How is BHD diagnosed?

BHD is suspected when a person has skin tumors (fibrofolliculomas) associated with BHD, especially if that person or their family members have a history of lung cysts, spontaneous pneumothorax, or kidney cancer. BHD is also suspected in families with multiple cases of kidney cancer, particularly if family members have had different types of kidney cancer or specific types of kidney cancer known to be associated with BHD. Genetic testing to look for mutations in the FLCN gene is available for people suspected of having BHD.

What are the estimated cancer risks associated with BHD?

BHD is associated with an increased risk for kidney cancer, particularly HOTs, chromophobe renal cell carcinoma (RCC), or oncocytoma. Clear cell, papillary, and unclassified tumors can occur too and generally are more aggressive variants when associated with BHD. (For more on the various types and cell types of kidney cancer, visit the Kidney Cancer section on this website.) The estimated risk for kidney cancer in people with BHD is around 15% to 30%.

What are the screening options for BHD?

There are no specific screening guidelines for BHD. Due to the risk of kidney cancer, some doctors suggest that individuals who have BHD or a family history of BHD have periodic cross sectional imaging, which is when sound waves are used to create a picture of the internal organs, of their kidneys, beginning after the age of 20. As ultrasound can miss such tumors since they can produce sounds similar to normal tissue (called isoechoic), most experts suggest periodic scans (every 2 years for screening) with either an abdominal computed tomography scan (CT or CAT) or magnetic resonance imaging (MRI). An initial evaluation by a dermatologist (a doctor specializing in skin problems) to evaluate the skin and a pulmonologist (a doctor specializing in lung problems) to evaluate any lung cysts are also suggested.

Screening guidelines may change over time as new technologies are developed and more is learned about BHD. It is important to talk with your health care team about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the health care team

If you are concerned about your risk for kidney cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing kidney cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have BHD, consider asking the following questions:

  • If I have had a collapsed lung/pneumothorax, could it be associated with a genetic condition?

  • Does my family history increase my risk of developing kidney cancer?

  • Are the skin tumors on me or on my family members consistent with a diagnosis of BHD?

  • Do you think I should have a cancer risk assessment? If so, will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing?

Related Resources

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

More Information

Kidney Cancer Association

National Cancer Institute

To find a genetic counselor in your area, ask your doctor or visit the following website:

National Society of Genetic Counselors