Is Birt-Hogg-Dubé syndrome hereditary?

Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic disorder that affects multiple organ systems in the body. It was first described in 1977 by Drs. Birt, Hogg, and Dubé, hence the name. BHDS is characterized by the development of benign skin tumors, lung cysts, and an increased risk of certain types of kidney tumors.

Genetic studies have shown that BHDS is caused by mutations in the Folliculin (FLCN) gene. This gene provides instructions for making a protein that is involved in regulating cell growth and division. In individuals with BHDS, mutations in the FLCN gene lead to the production of an abnormal or nonfunctional protein, which disrupts normal cellular processes.

Hereditary nature of BHDS:

BHDS is inherited in an autosomal dominant manner, which means that a person with a mutation in one copy of the FLCN gene has a 50% chance of passing the mutation on to each of their children. Both males and females can be affected by BHDS, and the severity of the symptoms can vary widely even among affected family members.

It is important to note that not everyone who inherits a mutation in the FLCN gene will develop BHDS or show symptoms of the syndrome. This phenomenon is known as reduced penetrance. The reasons behind reduced penetrance in BHDS are not yet fully understood, but it suggests that other genetic or environmental factors may influence the development and severity of the syndrome.

Diagnosis and clinical features:

The diagnosis of BHDS is typically based on a combination of clinical features, family history, and genetic testing. The most common clinical manifestations of BHDS include:

• Benign skin tumors: BHDS is often associated with the development of multiple fibrofolliculomas, which are small, flesh-colored or reddish-brown bumps on the skin. These tumors typically appear on the face, neck, and upper body.


• Lung cysts: Individuals with BHDS may develop multiple cysts in their lungs. These cysts are usually asymptomatic and are often discovered incidentally on imaging studies.


• Kidney tumors: BHDS is also associated with an increased risk of certain types of kidney tumors, including chromophobe renal cell carcinoma and oncocytoma. The age of onset and severity of kidney involvement can vary among affected individuals.

Management and treatment:

There is currently no cure for BHDS, and treatment mainly focuses on managing the symptoms and reducing the risk of complications. Regular monitoring and screening for kidney tumors are recommended for individuals with BHDS, as early detection can improve outcomes. Lung cysts are typically managed conservatively, but in some cases, intervention may be necessary if they cause symptoms or complications.

Genetic counseling is an essential component of the management of BHDS. Individuals with a family history of BHDS or those who have been diagnosed with the syndrome should consider seeking genetic counseling to understand the inheritance pattern, assess the risk of passing on the mutation to their children, and discuss available testing options.

Conclusion:

Birt-Hogg-Dubé syndrome is a rare genetic disorder caused by mutations in the FLCN gene. It is inherited in an autosomal dominant manner, with variable penetrance. BHDS is characterized by the development of benign skin tumors, lung cysts, and an increased risk of certain kidney tumors. While there is no cure for BHDS, regular monitoring and screening can help manage the symptoms and reduce the risk of complications. Genetic counseling is crucial for individuals with BHDS and their families to understand the inheritance pattern and make informed decisions.

by Diseasemaps