What Is Birt-Hogg-Dubé Syndrome? (2024)

Birt-Hogg-Dubé syndrome, also called BHD, is a genetic disease that impacts the skin, lungs, and kidneys. Changes in these tissues lead to various noncancerous (benign) skin growths, lung cysts, potential lung collapse (pneumothorax), and kidney growths that can be cancer.

BHD is rare, and most of the symptoms are non-life-threatening. They typically start appearing in young adulthood. This article will provide an overview of Birt-Hogg-Dubé syndrome, including causes, symptoms, and complications.

BHD Syndrome Causes

BHD is a genetic disease, which means it is caused by a change (mutation) in the body’s genetic code—the set of instructions within a gene that directs cells on how to make a specific protein. For BHD, this change is in the FLCN gene. The FLCN gene codes for a protein called folliculin.

Researchers aren’t sure exactly what this protein does, but they know it helps keep cells from growing into tumors. With a mutation of this gene, growths begin to appear as cells divide too quickly and uncontrollably.

How Is BHD Syndrome Inherited?

This genetic disease is inherited in an autosomal dominant fashion. "Autosomal" means that the faulty gene is on a chromosome other than X or Y, which determine the biological sex of a person, and so people of any sex have an equal chance of inheriting it. "Dominant" means that to have symptoms of BHD, the person only needs one copy of the mutated PLCN gene.

If someone has the mutated gene, their children have a 50% chance of inheriting it. Most cases of BHD develop this way, inherited from one parent.

It is also possible for BHD to develop without being inherited if the gene changes on its own—called a de novo mutation. This person may then pass down the mutated gene to their offspring.

If you have BHD and are worried about passing it down to your children, ask your healthcare provider about prenatal diagnosis or preimplantation genetic testing to see if the embryo has the mutated FLCN gene.

BHD Syndrome Symptoms

Symptoms of BHD are seen in several tissues:

• The skin can develop multiple noncancerous tumors: These can occur across the face, neck, and upper chest.
• The lungs can develop asymptomatic cysts that show up on imaging: People with BHD are also at an increased risk of their lungs spontaneously collapsing.
• The kidneys can develop growths: These can be benign or malignant (cancerous).

Skin symptoms of BHD develop starting around a person's 20s or 30s. The growths get bigger and spread over more of the body as the individual ages.

Several types of noncancerous tumors develop on the skin. These include:

• Fibrofolliculomas are small, skin-colored, dome-shaped growths that develop in the hair follicles.
• Acrochordons are skin tags, a common type of growth that can be skin-colored or dark in color and stick out from the skin's surface.
• Angiofibromas are made up of connective tissue and blood vessels and show up as small red bumps on the nose and cheeks.
• Epidermal cysts are closed sacs under the skin that contain dead skin cells and fluid. They can be felt as bumps under the skin and typically develop from damaged or blocked hair follicles.

These skin symptoms are very common in BHD patients. About 85% have skin growths, and 80% have fibrofolliculomas by age 40.

Lung symptoms of BHD include lung cysts, which are fluid- or air-filled sacs of tissue in the lungs. They don't usually cause any symptoms but can be seen on imaging. Changes in the lung tissues can also lead to an accumulation of air in the chest cavity that increases the risk of the lung spontaneously collapsing.

Kidney symptoms of BHD include a higher risk of developing cancerous or noncancerous kidney tumors. It may also increase the risk of developing other cancers, including those of the thyroid and parathyroid. Researchers are still studying these links.

Diagnosis

Diagnosis of BHD includes a detailed physical examination of the skin and any skin growths, a health and personal history, and a biopsy of the skin growths (taking a sample to be analyzed in the lab) to verify what kind of lesions they are.

Suggestive diagnostic criteria include:

• Two cutaneous growths or more that are clinically consistent with fibrofolliculoma/trichodiscoma and at least one confirmed to be a fibrofolliculoma
• Multiple cysts in both lungs, mainly in the basilar regions, with or without the person having a spontaneous pneumothorax (collapsed lung) by age 40, especially with a family history of such lung problems
• Chromophobe renal cell cancer in multiple spots on both kidneys, or mixed cell renal cell cancer, especially if the person is under 50 or has a family history of renal tumors
• A combination of these skin, lung, or kidney problems in the person or members of their family

A blood test can confirm a diagnosis of BHD through genetic testing. Genetic confirmation is important for the person and family members, who may not know they have it.

The symptoms of BHD can vary even within families. Some family members may have more severe symptoms than others. Still, no matter the outward signs, a person with BHD will be at an increased risk of cancer and will be able to pass on the mutated gene to their children.

After a positive genetic test, the healthcare provider will likely recommend some testing to check for symptoms.

These tests may include an ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) of the kidneys to check for growths. They may also recommend getting a chest X-ray and a colonoscopy to check for precancerous growths in the colon and rectum.

Risks

People with BHD and a genetic defect in the FLCN gene are at increased risk of developing skin growths, having their lung collapse, and developing tumors on their kidneys, which can be cancerous.

• Up to 85% of people with BHD develop skin growths—usually starting after the age of 20.
• More than 80% of people with BHD develop cysts in the lungs
• Up to one-third of people with BHD experience a collapsed lung multiple times. People with BHD have a 50 times higher risk of their lung collapsing without having sustained an injury to cause it.
• Somewhere between 15% and 30% develop kidney tumors—a risk about 7 times higher than their siblings without BHD.
• Other cancers linked to BHD include tumors in the salivary (parotid) glands, thyroid and parathyroid growths, colon polyps (precancerous growths), brain and spinal cord tumors, ovarian cysts, and other growths in the skin, lungs, eyes, and fatty tissue.

Outlook

Outlook for people with BHD is good, especially if the person keeps up with regular screenings to check for cancers and catch them early. While the medical community hasn't agreed on official guidelines for screening people with BHD, there are some recommendations a healthcare provider will likely pass along to a person with BHD, including:

• Have their skin examined one or two times a year to check for new growths and skin cancer
• Get annual abdominal imaging to check for kidney growths
• Check in with their healthcare provider about any new symptoms every year—including those that may indicate a problem with the parathyroid
• Get an annual ultrasound of the thyroid to check for tumors
• Start having colonoscopies to screen for colon cancer early—around or before age 40—depending on risk factors

Summary

BHD is a rare genetic condition linked to skin growths, lung cysts, and kidney tumors. Symptoms of BHD include bumps on the skin, lung collapse, and kidney cancer. With regular screenings for cancer, the outlook for people with BHD is positive.

While having skin growths and getting annual screenings for cancer aren’t pleasant, BHD usually isn't life-threatening. Catching cancer in its early stages can help you get effective treatments.

Knowing that you or your family members could have this genetic mutation is important so you can monitor symptoms. Get tested and let your family members know if you’re positive for the gene mutation so their healthcare providers can test them, too. Knowledge is power when you’re at a higher than average risk for cancers.