Is Birt-Hogg-Dubé syndrome hereditary?

Birt-Hogg-Dubé syndrome (BHD) is a hereditary genetic condition caused by pathogenic variants in the FLCN gene, which follows an autosomal dominant inheritance pattern. This means that an affected individual has a 50% chance of passing the gene mutation to each of their children, regardless of the child's biological sex.

Is Birt-Hogg-Dubé syndrome hereditary?

Yes, Birt-Hogg-Dubé syndrome is a hereditary condition, meaning it is passed down through families via genetic information. It is classified as an autosomal dominant disorder, which results from a mutation in the FLCN (folliculin) gene located on chromosome 17. Because it is dominant, only one copy of the altered gene—inherited from either parent—is sufficient to cause the syndrome. While most cases are inherited, it is possible for an individual to be the first in their family to have the condition due to a de novo (spontaneous) mutation that occurs during the formation of reproductive cells or early embryonic development.

What are the risks to family members?

For individuals diagnosed with Birt-Hogg-Dubé syndrome, understanding the inheritance risk is a critical component of family planning. Because the condition is autosomal dominant, the following statistical risks apply:

• Offspring: Each child of an affected parent has a 50% chance of inheriting the FLCN gene mutation.


• Siblings: If a parent has the mutation, each sibling of the affected individual also has a 50% chance of carrying the same mutation.


• Variable Expressivity: It is important to note that even within the same family, individuals with Birt-Hogg-Dubé syndrome may experience different symptoms, or varying degrees of severity, due to variable expressivity.

How is genetic testing and counseling utilized?

Genetic testing for Birt-Hogg-Dubé syndrome is performed via sequence analysis of the FLCN gene to identify pathogenic variants. Clinical geneticists generally recommend testing for individuals who present with characteristic skin lesions (fibrofolliculomas), recurrent pulmonary cysts, spontaneous pneumothorax, or renal tumors. Genetic counseling is essential for families, as it helps interpret test results, discusses the 50% inheritance probability, and reviews options for family planning, such as preimplantation genetic testing (PGT) for those undergoing in vitro fertilization. Currently, 114 people in the DiseaseMaps.org community have shared their experiences, providing a valuable network for those navigating these complex genetic conversations.

What is the role of prenatal and carrier testing?

Carrier testing is typically not applicable in the traditional sense because Birt-Hogg-Dubé syndrome is dominant; therefore, anyone who carries the mutation is considered affected, even if they are asymptomatic at the time of testing. Prenatal diagnosis is available for families who have identified a specific FLCN mutation. This can be performed through chorionic villus sampling (CVS) or amniocentesis during pregnancy. Families are encouraged to discuss these reproductive options with a certified genetic counselor to weigh the medical and ethical considerations specific to Birt-Hogg-Dubé syndrome.

Next steps

• Consult with a clinical geneticist to discuss genetic testing for yourself and your immediate family members.


• Connect with the 114 members of the DiseaseMaps.org community to share experiences and find support.


• Review your family medical history to identify relatives who may have had symptoms of pneumothorax or renal issues.


• Schedule an appointment with a nephrologist or pulmonologist familiar with Birt-Hogg-Dubé syndrome for routine surveillance.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment; always consult with your physician regarding your specific health situation.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Birt-Hogg-Dubé syndrome profile.


• Orphanet: Rare disease database entry for Birt-Hogg-Dubé syndrome (ORPHA:125).


• OMIM (Online Mendelian Inheritance in Man): FLCN gene entry #607273.


• The BHD Foundation: Resources for patients and families affected by Birt-Hogg-Dubé syndrome.