Birt-Hogg-Dubé Syndrome (BHDS) is a rare genetic condition that can affect various parts of the body, particularly the skin, lungs, and kidneys. In this article, we’ll break down the key aspects of BHDS in simple, easy-to-understand language. We’ll cover the different types of BHDS, its causes, symptoms, diagnostic tests, treatments, and medications, aiming to enhance readability, visibility, and accessibility for those seeking information on this condition.

Birt-Hogg-Dubé (BHD) syndrome is a rare complex genetic skin disorder (genodermatosis) characterized by the development of skin papules generally located on the head, face and upper torso. These benign (noncancerous) tumors of the hair follicle are called fibrofolliculomas. BHD syndrome also predisposes individuals to the development of benign cysts in the lungs, repeated episodes of a collapsed lung (pneumothorax) and increased risk for developing kidney neoplasia. BHD syndrome is caused by changes (pathogenic variants or mutations) in the FLCN gene and is inherited in an autosomal dominant pattern.

Types of Birt-Hogg-Dubé Syndrome

1. Full Syndrome: The full BHDS is the most common type and presents with a combination of skin lesions, lung cysts, and kidney tumors.
2. Partial Syndrome: In partial BHDS, individuals may have some, but not all, of the typical symptoms, which can vary in severity.

Causes of Birt-Hogg-Dubé Syndrome

BHDS is caused by changes (mutations) in a specific gene called FLCN (Folliculin). These mutations are usually inherited from a parent, but they can also occur spontaneously.

BHD syndrome is caused by changes (pathogenic variant or mutations) in the FLCN gene. The FLCN gene carries the instructions to produce (encode) folliculin, a protein whose precise function is not known, but which interacts with proteins that function in cellular pathways involved in cell growth, energy production and metabolism. The FLCN gene is a tumor suppressor gene, a gene that keeps cell growth in check or slows its growth, repairs damage to the DNA of cells and tells cells when to die, a normal process called apoptosis. Variants in a tumor suppressor gene often predispose individuals to develop cancer, but having a gene variant does not absolutely guarantee development of the disease.

The predisposition to develop Birt-Hogg-Dubé syndrome is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new gene change in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

In some individuals, the predisposition to the disorder is due to a spontaneous (de novo) gene change that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.

Symptoms of Birt-Hogg-Dubé Syndrome

1. Skin Lesions: BHDS can cause small, noncancerous skin tumors that appear on the face, neck, and upper body.
2. Lung Cysts: Individuals with BHDS often develop cysts (small sacs filled with air) in their lungs, which can lead to breathing difficulties.
3. Kidney Tumors: Kidney tumors, usually noncancerous, can develop in people with BHDS and may require medical attention.
4. Frequent Lung Infections: Lung infections can be more common in BHDS patients due to lung cysts.
5. Pneumothorax: BHDS can increase the risk of pneumothorax, a condition where air leaks into the space between the lungs and chest wall, causing chest pain and breathing problems.
6. Overactive Sweat Glands: Some individuals with BHDS may have overactive sweat glands, leading to excessive sweating.
7. Facial Tics: Rarely, facial tics or involuntary muscle contractions may occur in BHDS patients.
8. Digestive Symptoms: BHDS can cause digestive issues, such as diverticulosis or diverticulitis.
9. Vision Problems: In a few cases, BHDS can lead to eye problems like cataracts.
10. Hearing Loss: Hearing loss can be a symptom of BHDS in some individuals.
11. Lipomas: Benign fatty lumps known as lipomas may develop in BHDS patients.
12. Hair Follicle Abnormalities: Some people with BHDS may have hair follicle abnormalities, resulting in unusual hair growth patterns.
13. Psychological Impact: Coping with BHDS can sometimes lead to psychological stress and anxiety.
14. Infertility: BHDS may affect fertility in some individuals.
15. Increased Risk of Cancer: While kidney tumors associated with BHDS are usually noncancerous, there is a slightly increased risk of developing kidney cancer.
16. Other Skin Issues: Skin problems like acne or excessive hair growth can occur in BHDS patients.
17. Sleep Apnea: Sleep apnea, a condition where breathing repeatedly stops and starts during sleep, can be more common in BHDS individuals.
18. Bone Cysts: Rarely, cysts can develop in the bones of people with BHDS.
19. Gastrointestinal Symptoms: BHDS may cause gastrointestinal symptoms like bloating or abdominal discomfort.
20. Fatigue: Some BHDS patients experience persistent fatigue.

Diagnostic Tests for Birt-Hogg-Dubé Syndrome

1. Genetic Testing: A genetic test can identify mutations in the FLCN gene, confirming the diagnosis of BHDS.
2. Skin Biopsy: A small sample of a skin lesion may be removed and examined under a microscope to check for BHDS-related abnormalities.
3. CT Scans: Computed tomography (CT) scans of the chest and abdomen can reveal lung cysts and kidney tumors.
4. Kidney Imaging: Imaging tests like MRI or ultrasound can detect kidney tumors.
5. Lung Function Tests: These tests assess lung capacity and function, helping diagnose lung cysts.
6. Biopsy of Kidney Tumors: If a kidney tumor is found, a biopsy may be performed to determine if it is cancerous.
7. Eye Exams: An ophthalmologist may conduct an eye exam to check for any BHDS-related eye issues.
8. Hearing Tests: Audiologists can evaluate hearing loss.
9. Endoscopy: For gastrointestinal symptoms, an endoscopy may be done to examine the digestive tract.
10. Sleep Studies: Sleep studies can diagnose sleep apnea.
11. Bone Scans: In rare cases, bone scans may be used to detect bone cysts.
12. Blood Tests: Blood tests can help monitor kidney function and overall health.

Treatments for Birt-Hogg-Dubé Syndrome

1. Skin Lesions: Skin lesions can be removed through minor surgical procedures for cosmetic reasons.
2. Lung Cysts: Treatment for lung cysts depends on their size and impact on lung function. In some cases, doctors may recommend observation, while others may require intervention.
3. Kidney Tumors: Small, noncancerous kidney tumors may be monitored regularly, while larger or cancerous tumors may require surgical removal.
4. Pneumothorax: Treatment for pneumothorax involves removing the trapped air from the chest cavity, often through a chest tube.
5. Management of Digestive Issues: Gastrointestinal symptoms can be managed with dietary changes and medications.
6. Eye Problems: Cataracts can be treated with surgery, if necessary.
7. Hearing Aids: Hearing loss can be managed with hearing aids.
8. Sleep Apnea: Sleep apnea can be treated with lifestyle changes, continuous positive airway pressure (CPAP) therapy, or surgery.
9. Psychological Support: Mental health support and counseling can help individuals cope with the emotional impact of BHDS.
10. Fertility Consultation: Individuals concerned about fertility issues can consult with fertility specialists.
11. Cancer Monitoring: Regular monitoring and screenings can detect kidney cancer at an early, more treatable stage.
12. Medications: Some medications may be prescribed to manage specific symptoms or complications of BHDS.

Medications Used in Birt-Hogg-Dubé Syndrome

1. Pain Relievers: Over-the-counter or prescription pain relievers can help manage discomfort from lung cysts or surgery.
2. Antibiotics: Antibiotics treat lung infections that may occur due to lung cysts.
3. Anti-anxiety Medications: In some cases, anti-anxiety medications can help manage psychological distress.
4. Acne Medications: Acne medications may be prescribed for skin issues associated with BHDS.
5. Hormonal Therapy: Hormonal therapy can be used to manage excessive hair growth or other hormone-related symptoms.
6. Hearing Aid Devices: Hearing aids can help individuals with hearing loss.
7. CPAP Machines: Continuous positive airway pressure (CPAP) machines are used to treat sleep apnea.
8. Bone Medications: Rarely, medications may be prescribed to manage bone cysts.

Some instances of a lung collapse do not require treatment and the air is absorbed over several days. In some patients, treatment is necessary. Treatment of a collapsed lung is intended to remove the air surrounding the lungs, allowing the lungs to re-inflate. A tube is inserted into the chest to allow the air or gas to escape (aspiration). In cases where repeated lung collapses occur, surgery may be necessary.

Surgery may also be necessary in individuals with renal neoplasia. Surgeons need to remove the kidney neoplasm, so it does not grow larger and spread (metastasis). They may also remove part or all of a kidney (nephrectomy) if the tumor burden is extensive. The main objective of surgery in individuals with renal neoplasia is to preserve as much kidney tissue as possible, thereby preserving as much of the kidney function as possible. Since individuals with BHD may have multiple surgeries for multiple tumors over their lifetime, one effective management practice has been to wait and remove the largest tumor when it reaches 3 cm in diameter by nephron-sparing surgery.

Individuals with BHD syndrome without renal neoplasia should be periodically imaged to monitor tumor development (recommended at 2-to-3-year intervals).

Conclusion

Birt-Hogg-Dubé Syndrome is a complex genetic condition that can affect multiple aspects of a person’s health. While there is no cure, individuals with BHDS can manage their symptoms and lead fulfilling lives with proper medical care and support. Early diagnosis, regular monitoring, and a multidisciplinary approach involving various medical specialists are key to effectively managing BHDS and improving the quality of life for affected individuals. If you suspect you or a loved one may have BHDS, it’s essential to seek medical attention and genetic testing to confirm the diagnosis and initiate appropriate care.