Birt-Hogg-Dubé syndrome

This page was reviewed under our medical and editorial policy by

Eric Fowler, MS, LCGC, Manager, Clinical Genetics, Western Region & Licensed Certified Genetic Counselor

This page was reviewed on August 20, 2021.

If someone has had more than one of these symptoms—multiple lung cysts, growths on the skin, and kidney cancer/tumor—doctors may advise searching for an underlying cause. This may include genetic testing to see whether a rare inherited condition called Birt-Hogg-Dubé syndrome may be responsible.

Birt-Hogg-Dubé syndrome, also known as BHDS, is caused by a genetic change, or a mutation, in a specific gene. This condition also increases the risk of a collapsed lung without injury or trauma.

What is Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome is a genetic condition that can be passed from parent to child due to a mutation in a gene found in all the body’s cells. This mutation causes a range of issues, including:

  • Noncancerous growths in hair follicles (fibrofolliculomas) in the face, neck and chest
  • Increased risk of developing multiple noncancerous kidney tumors (oncocytomas) or kidney cancer (chromophobe, clear cell, and less commonly, mixed chromophone/oncocytoma or papillary)
  • Multiple cysts that may cause a lung to deflate (pneumothorax)
  • Other growths, benign tumors and cancers may occur, but to a lesser extent

Not everyone with Birt-Hogg-Dubé syndrome shows all the symptoms. They may show up in varying degrees in different people with BHDS. Symptoms tend to first arise in young adulthood, usually starting with the development of skin growths on the face and neck.

Causes of BHD

Birt-Hogg-Dubé syndrome is caused by a mutation in a gene called FLCN. Genes are the code that the body’s cells use to make proteins. Proteins make up most of the body’s structures and are involved in most of its actions—tasks such as storing memories, digesting food and propelling movement.

The FLCN gene is responsible for making a protein called folliculin. When the folliculin gene is unable to make a protein that works, growths can develop in the skin and kidneys. Researchers aren’t sure what this protein does normally, but it may act as a check on cell growth to stop tumors from forming.

Risk factors for BHD

Birt-Hogg-Dubé syndrome is extremely rare. About 600 families have been reported to carry the gene in total, though it may be underdiagnosed, according to the National Organization for Rare Disorders (NORD).

The syndrome is inherited in a dominant fashion, so a person needs only one abnormal copy of the FLCN gene to be symptomatic. There are two ways in which a person may have Birt-Hogg-Dubé syndrome:

  • Inheriting BHDSfrom a parent (Each child of someone with BHDS has a 50 percent, or 1 in 2, chance of inheriting in the condition.)
  • Being the first person in a family to have BHDS (Not all FLCN mutations are inherited. Mutations that are not inherited, called de novo mutations, may happen in the FLCN gene, which then can be passed to any children of that person.)

The children of someone with Birt-Hogg-Dubé syndrome should consider genetic counseling and testing by age 18-20.

Symptoms of BHD

Skin tumors: People with Birt-Hogg-Dubé syndrome develop skin growths known as fibrofolliculomas. These are small (2-3 mm), whitish or flesh-colored bumps that grow from hair follicles and appear in the skin of the face (including the scalp, inside the mouth and around the ears), neck and upper chest. Up to 85 percent of people with Birt-Hogg-Dubé develop skin growths, according to the NORD. They typically show up in young adulthood and continue to increase in number as the person ages. Skin cancers have been seen in people with BHDS, and risks for skin cancer may be increased.

Lung cysts: Pulmonary cysts are pockets of air (and less often, fluid) that develop inside the lung tissue, usually around the edges where the lungs meet the chest cavity. These cysts don’t usually cause symptoms in people with Birt-Hogg-Dubé syndrome, but they increase the risk of having the lungs collapse. Scientists aren’t sure why an abnormal FLCN gene leads to more lung cysts and collapsed lungs, but almost all people with BHDS seem to have them, according to research reported in Familial Cancer.

Spontaneous pneumothorax: If the lung cysts become large, they may cause the sudden collapse of the lung. A collapsed lung, or spontaneous pneumothorax, is usually preceded by an abnormal buildup of air between the lungs and the chest cavity. The air buildup puts pressure on the lungs, making it difficult to take in enough air to expand them, so part of the lung may stay compressed. Symptoms of a collapsed lung include:

  • Chest pain
  • Discomfort when breathing
  • Shortness of breath

Kidney tumors: People with Birt-Hogg-Dubé syndrome may develop a type of kidney tumor called an oncocytoma. These noncancerous growths don’t usually cause symptoms and are discovered by chance. According to the Genetic and Rare Diseases Information Center, 1 in 3 people with a renal oncocytoma will have symptoms, which may include:

  • Pain in the abdomen or flank
  • Blood in urine
  • Mass in the abdomen

People with Birt-Hogg-Dubé syndrome may develop multiple oncocytomas in both kidneys. They don’t usually require treatment, but because it can be hard to differentiate between these benign growths and more dangerous cancerous growths, doctors may want to perform surgery to remove and test them.

Kidney cancer: About 15 percent to 30 percent of people with Birt-Hogg-Dubé syndrome develop kidney cancer, according to the NORD. Kidney cancers occur on average when people with BHDS are in their 50s, but have been reported as by the early 30s. Kidney cancer symptoms include:

  • Abdominal swelling
  • Pain in the back or abdomen
  • Blood in urine
  • Unintended weight loss

Diagnosing BHD

Finding a mutation in the FLCN gene would confirm a Birt-Hogg-Dubé syndrome diagnosis. However, BHDS may also be diagnosed if a person has five or more fibrofolliculomas with at least one confirmed with a biopsy, or two or more of the following:

  • Multiple, often many, lung cysts
  • Kidney cancer before age 50
  • More than one kidney cancer diagnosis
  • Renal cancer of the mixed chromophobe.oncocytic type
  • A parent, sibling or child with BHDS

Medical management for people with BHDS

Lungs: After a diagnosis of Birt-Hogg-Dubé syndrome, the lungs should be checked for cysts. An imaging test called a computed tomography (CT) scan is used to take pictures of tissues inside the lungs. If many lung cysts are detected, it’s important to notify doctors of symptoms that may indicate a possible lung collapse.

People with BHDS should also avoid certain activities that could lead to lung collapse and ask their doctor or lung specialist (pulmonologist) for specific advice. These activities include smoking cigarettes and scuba diving.

Sometimes, a collapsed lung doesn’t require treatment. When it does, this may involve inserting a tube into the chest cavity to relieve the pressure of trapped air and let the lungs reinflate. If it keeps happening, surgery may be recommended.

Kidneys: Starting at age 20, people with BHDS should have annual imaging studies of their kidneys to screen for cancers, with magnetic resonance imaging (MRI) being the preferred test. Kidney cancer would likely be treated with surgery to remove the tumor and then possibly with additional cancer treatments such as chemotherapy and radiation therapy.

Skin: Those BHDS should get full skin exams every six to 12 months.

Salivary (parotid) glands: Some people with BHDS have developed tumors of the salivary or parotid glands, which are located just in front of the ears and from the cheek down to the jawline. Any swelling or pain should be reported to a doctor.

Thyroid gland: People with BHDS may be at increased risk of developing thyroid cancer. Annual ultrasounds may be considered.

Colon: Colon cancer has been diagnosed in some families with BHDS, but whether they have an increased risk is uncertain. People with BHDS should talk to their physicians about when they should begin screening for colon cancer.

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