Birt-Hogg-Dubé syndrome (BHDS)
Birt-Hogg-Dubé syndrome (BHDS) is a rare genetic condition primarily caused by mutations in the FCLN gene, which is responsible for producing folliculin, a protein that acts as a tumor suppressor. Individuals with BHDS may experience growths on the skin, known as fibrofolliculomas, and a significant predisposition to developing kidney tumors, including both benign and cancerous types. While the incidence of kidney cancer in BHDS patients is estimated to be around 15%, over 80% of affected individuals may develop lung cysts. BHDS symptoms typically manifest between a person's late twenties and early forties, although some individuals may remain asymptomatic. Diagnosis often involves skin lesion biopsies and imaging studies to detect kidney tumors and lung cysts. Currently, there is no definitive medical treatment for the skin lesions, and surgical intervention is the primary approach for managing kidney tumors. Regular monitoring and screening are recommended for individuals with BHDS to manage the associated risks effectively. Understanding this syndrome is crucial for those with a family history or concerning symptoms, as genetic counseling can provide valuable insights into risk factors and management strategies.
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Birt-Hogg-Dubé syndrome (BHDS)
Related conditions: Renal cell carcinoma, pulmonary cysts
Definition: Birt-Hogg-Dubé syndrome (BHDS) is a rare, genetically linked syndrome named after the three Canadian doctors who first identified it as a skin disorder. It consists of three types of benign skin growths: fibrofolliculomas, white or flesh-colored tumors that occur in hair follicles; trichodiscomas, overgrowths of tissues in hair disks; and acrochordons, commonly called skin tags. These growths are typically found on the face, neck, chest, and scalp.
Since the identification of BHDS in 1977, further study of patients with the syndrome has revealed additional abnormal conditions that characteristically develop in affected individuals. The most common of these conditions include benign and cancerous kidney tumors, lung cysts, and spontaneous pneumothorax.
Risk factors: BHDS is genetically linked, meaning that it is associated with a defect in one or more genes. Although in most cases the gene responsible for BHDS has been passed through families, evidence of genetic mutation in people with no familial link has also been identified. People with a defective gene and who also smoke have a higher risk of developing kidney cancer.
Etiology and the disease process: BHDS is caused by a mutation in the gene that is responsible for the body’s production of folliculin, a protein that acts as a tumor suppressor. When folliculin is absent or not functioning properly, it cannot control cellular growth and division, which leads to tissue overgrowth and the formation of tumors. Folliculin is present in many types of tissues but is primarily found in skin, lung, and kidney cells.
The folliculin gene, otherwise know as FCLN, is located on chromosome 17p11.2. Normally, during conception, the body receives two copies of every gene, one from the mother and one from the father. In BHDS, a single defective copy of the gene, from either the mother or the father, results in a person’s being affected by the disease.
BHDS usually begins with the formation of skin growths. As the disease progresses, these growths increase in number and size. Slow-growing kidney tumors can develop as single or multiple tumors in one or both kidneys. Several types of tumors have been associated with BHDS, including benign tumors such as renal oncocytomas and cancerous tumors such as chromophobe renal carcinoma and clear cell carcinoma. Benign tumors often become cancerous as the disease progresses. Research into kidney tumors associated with BHDS indicates that a genetic mutation occurs in the second gene of affected kidney cells, producing two defective genes, which allows these tumors to grow.
Incidence: BHDS is very rare, having been identified only in about four hundred families worldwide. A precise incidence rate is unknown because people are not routinely tested for the presence of the FCLN gene. There is no indication that race or gender influences a person’s risk of having the gene or developing the disease. The typical age that a person begins to display signs of BHDS is between the late twenties and early forties. The incidence of kidney cancer in people with BHDS may be as low as 15 percent; however, the incidence of lung cysts is estimated to be more than 80 percent.
Symptoms: Although some people with BHDS have no noticeable symptoms of the disease, the development of fibrofolliculomas or acrochordons is usually the first indication that the person is affected. Initially looking like small, white pimples, fibrofolliculomas typically become larger and more prolific as time passes. The development of polyps in the mouth or colon may also indicate BHDS and should be investigated further. Lung cysts, which usually do not cause respiratory problems, or lung cancer may be detected during routine examinations or testing for other conditions. Multiple or bilateral kidney tumors are often the first indication of BHDS.
Screening and diagnosis: Several recurrent tests are recommended for people with BHDS and those with family members who have BHDS. Recommendations include an annual kidney ultrasound and chest x-ray, computed tomography scanning or magnetic resonance imaging every two years, and biopsies of suspicious skin growths. DNA (deoxyribonucleic acid) testing to check for genetic alterations should be considered for individuals who have family members with the disease. Genetic counseling should precede any such testing.
The disease is typically diagnosed after skin lesion biopsies are positive for fibrofolliculomas or when multiple kidney tumors and lung cysts are identified.
Treatment and therapy: There is no specific medical treatment recommended for the skin tumors associated with BHDS. Surgical removal, electrodesiccation, and dermabrasion have been used without long-term success, as the growths recur. A relatively new procedure for BHDS-related skin tumors is laser skin resurfacing, which has been successful in several cases; however, long-term results are unknown.
Both benign and cancerous kidney tumors are removed surgically. However, new tumors often form in place of the ones removed. When possible, only part of the kidney is removed to prolong the patient’s kidney function. Experimental treatments to destroy the cancer cells may be used on recurrent tumors. These include cryoablation, freezing the tumor, and radio frequency ablation, killing the tumor with heat.
Prognosis, prevention, and outcomes: The prognosis for BHDS depends on whether kidney cancer develops and the success of its treatment. BHDS cannot be prevented.
Bibliography
“Birt-Hogg-Dubé Syndrome: Research and Support.” Bhdsyndrome.org. BHD Foundation, 2013. Web. 1 Oct. 2014.
Lindor, Noralane M., et al. “Birt-Hogg-Dubé Syndrome: An Autosomal Dominant Disorder with Predisposition to Cancers of the Kidney, Fibrofolliculomas, and Focal Cutaneous Mucinosis.” International Journal of Dermatology 40.10 (2001): 653–56. Print.
Pavlovich, C. P., et al. “Renal Tumors in the Birt-Hogg-Dubé Syndrome.” American Journal of Surgical Pathology 26 (2002): 1542–52.
Pomery, Chris. DNA and Family History. Toronto: Dundurn, 2004. Print.
Schmidt, Laura S. "Birt-Hogg-Dubé Syndrome: From Gene Discovery to Molecularly Targeted Therapies." Familial Cancer 12.3 (2013): 357–64. MEDLINE Complete. Web. 1 Oct. 2014
Schub T., and L. Buckley. "Birt-Hogg-Dube Syndrome." CINAHL Nursing Guide. Nursing Reference Center Plus, 2013. Web. 1 Oct. 2014.