What is Birt-Hogg-Dubé syndrome

TL;DR: Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder characterized by the development of benign skin tumors, recurrent collapsed lungs (pneumothorax), and an increased risk of developing kidney tumors. It is caused by mutations in the FLCN gene and follows an autosomal dominant inheritance pattern, meaning a single copy of the mutated gene is sufficient to cause the condition.

What is Birt-Hogg-Dubé syndrome and how does it affect the body?

Birt-Hogg-Dubé syndrome is a multisystem genodermatosis, meaning it affects multiple body systems, specifically the skin, lungs, and kidneys. While the syndrome is often identified through characteristic skin findings, the clinical significance lies primarily in the management of pulmonary and renal health. Individuals with Birt-Hogg-Dubé syndrome typically present with fibrofolliculomas (small, white, dome-shaped papules on the face, neck, and upper torso), which are benign hair follicle tumors. Beyond the skin, the lungs are often affected by the formation of multiple cysts that can rupture, leading to a spontaneous pneumothorax. Additionally, there is a lifelong increased risk of renal cell carcinoma, which necessitates ongoing clinical surveillance.

What causes Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome is caused by pathogenic variants in the FLCN gene, which provides instructions for making a protein called folliculin. This protein acts as a tumor suppressor, helping to regulate cell growth and division. When the FLCN gene is mutated, the body loses this regulatory check, leading to the abnormal tissue growth observed in the skin, lungs, and kidneys. Because Birt-Hogg-Dubé syndrome is inherited in an autosomal dominant fashion, each child of an affected parent has a 50% chance of inheriting the mutation.

Who is affected by Birt-Hogg-Dubé syndrome?

Birt-Hogg-Dubé syndrome is considered a rare condition, though its exact prevalence remains unknown because it is frequently underdiagnosed or misdiagnosed due to the variability of symptoms. It affects both males and females equally across all ethnic backgrounds. Symptoms usually emerge in adulthood, typically between the ages of 20 and 40, though the timing of skin lesions and pulmonary symptoms can vary significantly between family members. Within the DiseaseMaps.org community, 114 people with Birt-Hogg-Dubé syndrome have joined to share their personal experiences, highlighting the importance of patient-led advocacy in understanding this rare condition.

What differentiates Birt-Hogg-Dubé syndrome from other conditions?

Distinguishing Birt-Hogg-Dubé syndrome from other hereditary cancer syndromes requires a careful review of clinical and family history. Key distinguishing features include:

• Skin findings: The presence of multiple fibrofolliculomas is a hallmark of Birt-Hogg-Dubé syndrome, which helps clinicians differentiate it from other renal tumor syndromes like Tuberous Sclerosis or Von Hippel-Lindau disease.


• Pulmonary cysts: The specific appearance and distribution of lung cysts in Birt-Hogg-Dubé syndrome are often distinct on high-resolution CT scans.


• Renal tumor histology: Kidney tumors associated with Birt-Hogg-Dubé syndrome often have a unique "hybrid" appearance, containing features of both chromophobe renal cell carcinoma and oncocytoma.

Next steps

• Consult a clinical geneticist to discuss genetic testing for the FLCN gene if you suspect Birt-Hogg-Dubé syndrome.


• Schedule baseline and periodic renal imaging (MRI is preferred over CT to minimize radiation) with a urologist familiar with hereditary kidney cancer syndromes.


• Connect with the DiseaseMaps.org community to share experiences with others living with Birt-Hogg-Dubé syndrome.


• Consult a pulmonologist if you experience shortness of breath or have a family history of recurrent pneumothorax.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

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


• Orphanet: Birt-Hogg-Dube syndrome (ORPHA:124).


• OMIM (Online Mendelian Inheritance in Man): Birt-Hogg-Dube syndrome (#135150).


• The BHD Foundation: Research and patient support resources for Birt-Hogg-Dube syndrome.