What are the other Names for this Condition? (Also known as/Synonyms)

• Fibrofolliculomas with Trichodiscomas and Acrochordons
• Hornstein-Birt-Hogg-Dubé Syndrome
• Hornstein-Knickenberg Syndrome

What is Birt-Hogg-Dubé Syndrome? (Definition/Background Information)

• Birt-Hogg-Dubé Syndrome (BHDS) is a rare, complex, genetic disorder with three main clinical findings:
  • Non-cancerous (benign) skin tumors 
  • Lung cysts and/or history of pneumothorax (collapsed lung)
  • Various types of renal tumors
• Fibrofolliculomas are a type of benign skin tumor specific to BHDS. They typically occur on the face, neck, and upper torso
• Most people with BHDS also have multiple cysts in both lungs that can be seen on high-resolution chest CT scan. While these cysts usually do not cause any symptoms, they put people at increased risk for spontaneous pneumothorax
• BHDS is caused by mutations in the FLCN gene. The condition is inherited in an autosomal dominant fashion

(Source: Birt-Hogg-Dube Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Birt-Hogg-Dubé Syndrome? (Age and Sex Distribution)

• Birt-Hogg-Dubé Syndrome is a rare congenital disorder. The exact prevalence is not known, but it estimated that the disorder occurs at a frequency of 1:200,000, with about 100 affected families being reported in the scientific literature
• The presentation of symptoms may occur in adulthood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Birt-Hogg-Dubé Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Birt-Hogg-Dubé Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for BHDS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Birt-Hogg-Dubé Syndrome? (Etiology)

• Birt-Hogg-Dubé Syndrome develops as a result of mutation(s) in the FLCN gene
• The disorder is inherited in an autosomal dominant manner

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Birt-Hogg-Dubé Syndrome?

The signs and symptoms of Birt-Hogg-Dubé Syndrome may include:

Very frequently present symptoms in 80-99% of the cases:

• Emphysema
• Papule
• Skin tags

Frequently present symptoms in 30-79% of the cases:

• Abnormality of retinal pigmentation
• Multiple lipomas
• Pulmonary sequestration

Occasionally present symptoms in 5-29% of the cases:

• Medullary thyroid carcinoma
• Parathyroid adenoma
• Pneumothorax
• Renal cell carcinoma

Additional signs and symptoms in some affected individuals:

• Abnormality of abdomen morphology
• Abnormality of the hair
• Fibrofolliculoma
• Renal cyst
• Spontaneous pneumothorax

(Source: Birt-Hogg-Dube Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Birt-Hogg-Dubé Syndrome Diagnosed?

Birt-Hogg-Dubé Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Birt-Hogg-Dubé Syndrome?

The complications of Birt-Hogg-Dubé Syndrome may include:

• Severe chest pain
• Hypotension (drop in blood pressure) due to pneumothorax
• Tension pneumothorax: Air build up in the lung puts pressure on the heart and on the other lung. This is a medical emergency and requires urgent treatment
• Respiratory distress 
• Compromised kidney function

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Birt-Hogg-Dubé Syndrome Treated?

• Birt-Hogg-Dubé Syndrome is an inherited condition, and there is no cure for the condition
• The treatment is usually given to manage the signs and symptoms and any complication that develops

How can Birt-Hogg-Dubé Syndrome be Prevented?

Birt-Hogg-Dubé Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Avoiding situations with drastic pressure changes (such as scuba diving), piloting airplanes, and cigarette smoking may aid in preventing collapsed lungs in affected individuals

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Birt-Hogg-Dubé Syndrome? (Outcomes/Resolutions)

• The prognosis of Birt-Hogg-Dubé Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Birt-Hogg-Dubé Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/