Birt-Hogg-Dubé syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Birt-Hogg-Dubé syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals.

Birt-Hogg-Dubé syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dubé syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dubé syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the FLCN gene cause Birt-Hogg-Dubé syndrome. This gene provides instructions for making a protein called folliculin. The normal function of this protein is unknown, but researchers believe that it may act as a tumor suppressor. Tumor suppressors prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the FLCN gene may interfere with the ability of folliculin to restrain cell growth and division, leading to uncontrolled cell growth and the formation of noncancerous and cancerous tumors. Researchers have not determined how FLCN mutations increase the risk of lung problems, such as pneumothorax.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered FLCN gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Less commonly, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family.

Having a single mutated copy of the FLCN gene in each cell is enough to cause the skin tumors and lung problems associated with Birt-Hogg-Dubé syndrome. However, both copies of the FLCN gene are often mutated in the kidney tumors that occur with this condition. One of the mutations is inherited from a parent, while the other occurs by chance in a kidney cell during a person's lifetime. These genetic changes disable both copies of the FLCN gene, which allows kidney cells to divide uncontrollably and form tumors.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Birt-Hogg-Dubé syndrome is rare; its exact incidence is unknown. This condition has been reported in more than 400 families.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Fibrofolliculoma · Very frequent (99-80%)

Fibrofolliculoma is a clinically asymptomatic, 2-4 mm, skin-colored, dome-shaped smooth papule. It usually arises in the form of multiple lesions in adults in different areas such as the scalp, forehead, face, and neck. According to histology, the lesion is a fibrotic hamartoma characterized by infundibular epithelial proliferation and perifollicular fibrous proliferation.

Skin tags · Very frequent (99-80%)

Cutaneous skin tags also known as acrochorda or fibroepithelial polyps are small benign tumors that may either form secondarily over time primarily in areas where the skin forms creases, such as the neck, armpit or groin or may also be present at birth, in which case they usually occur in the periauricular region.

Multiple pulmonary cysts · Frequent (79-30%)

The presence of multiple lung cysts.

Spontaneous pneumothorax · Frequent (79-30%)

Pneumothorax occurring without traumatic injury to the chest or lung.

Repeated pneumothoraces · Frequent (79-30%)

Angiofibromas · Occasional (29-5%)

Angiofibroma consist of many often dilated vessels.

Collagenoma · Occasional (29-5%)

A rare hamartomatous malformation characterized by the predominant proliferation of normal collagen fibers and normal, decreased, or increased elastic fibers. Collagenomas may be solitary or multiple, sporadic, acquired or inherited.

Cutaneous melanoma · Occasional (29-5%)

The presence of a melanoma of the skin.

Epidermoid cyst · Occasional (29-5%)

Nontender, round and firm, but slightly compressible, intradermal or subcutaneous cyst measuring 0.5-5 cm in diameter. Epidermal cysts are intradermal or subcutaneous tumors, grow slowly and occur on the face, neck, back and scrotum. They usually appear at or around puberty, and as a rule an affected individual has one solitary or a few cysts. A central, dark comedone opening (punctum) may be present.

Medullary thyroid carcinoma · Occasional (29-5%)

The presence of a medullary carcinoma of the thyroid gland.

Multiple lipomas · Occasional (29-5%)

The presence of multiple lipomas (a type of benign tissue made of fatty tissue).

Neoplasm · Occasional (29-5%)

An organ or organ-system abnormality that consists of uncontrolled autonomous cell-proliferation which can occur in any part of the body as a benign or malignant neoplasm (tumor).

Oral mucosal papule · Occasional (29-5%)

A small (less than 5 mm in diameter), elevated, circumscribed, solid, palpable mass located in thte mucosa of the oral cavity.

Parathyroid adenoma · Occasional (29-5%)

A benign tumor of the parathyroid gland that can cause hyperparathyroidism.

Other findings in the same source

From: Orphanet

Additional reported features include Pneumothorax (Occasional (29-5%)); Renal cell carcinoma (Occasional (29-5%)); Renal cyst (Occasional (29-5%)); Salivary gland oncocytoma (Occasional (29-5%)); Thyroid cyst (Occasional (29-5%)); Thyroid nodule (Occasional (29-5%)); Trichodiscoma (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Birt-Hogg-Dubé syndrome is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Birt-Hogg-Dubé syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.