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March 2015

Birt-Hogg-Dubé Syndrome in an African Patient and a Novel Mutation in the FLCN Gene

Author Affiliations
  • 1Department of Dermatology, Drexel University College of Medicine, Philadelphia, Pennsylvania

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Dermatol. 2015;151(3):348-349. doi:10.1001/jamadermatol.2014.3720

Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant condition caused by mutations in the FLCN gene, is characterized by fibrofolliculomas, spontaneous pneumothorax, and renal cell carcinoma. Herein, we report the first case to our knowledge of BHDS in an African patient.

Report of a Case

A 53-year-old man from Somalia with a history of hypertension presented with multiple asymptomatic bumps on his face that appeared progressively over time. He denied having a personal or family history of similar lesions, renal cell carcinoma, spontaneous pneumothorax, or other pulmonary disease. Physical examination revealed diffuse flesh-colored, dome-shaped and pedunculated papules on the face, neck, upper back, chest, arms, and axillary folds (Figure 1). Histopathologic analysis of biopsy specimens taken from the left jawline (Figure 2) and left forearm were consistent with fibrofolliculoma and trichodiscoma, respectively. Genetic test results were positive for a novel nonsense heterozygous mutation p.Glu410Stop (E410X) in exon 11 of the FLCN gene. The patient was treated with shave removal of the lesions that were particularly disfiguring. At last follow-up, he was undergoing evaluation for renal and pulmonary disease.

Figure 1.
Image not available
Multiple Dome-Shaped Papules on the Face of an African Man

Diffuse flesh-colored, dome-shaped and pedunculated papules were also found on the neck, upper back, chest, arms, and axillary folds.

Figure 2.
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Biopsy Specimen From the Left Jawline

Dilated follicular structure containing laminated keratin and anastomosing epithelial strands radiates from the follicle with surrounding fibrous stroma (hematoxylin-eosin, original magnification ×40).


Birt-Hogg-Dubé syndrome was originally characterized by the triad of fibrofolliculomas, trichodiscomas, and acrochordons. The lesions usually appear after the second decade of life. Clinically, fibrofolliculomas and trichodiscomas are indistinguishable; both present as firm dome-shaped papules predominantly involving the face, scalp, and neck. However, skin findings may be absent in some patients. One of 2 major criteria proposed to diagnose BHDS is the presence of 5 or more fibrofolliculomas or trichodiscomas with 1 confirmed histologically.1

Histologically, fibrofolliculomas, trichodiscomas, and acrochordons were initially described as separate entities. However, many authorities now believe that all 3 are variants of a fibrofolliculoma, and the histopathologic distinction is related to differences in sectioning techniques.2 Fibrofolliculomas are characterized by anastomosing epithelial strands radiating from a dilated hair follicle within a fibrous stroma.

Birt-Hogg-Dubé syndrome has an autosomal dominant pattern of inheritance and is caused by germline mutations in the FLCN gene, which is located on chromosome 17p11.2. This gene encodes for the folliculin protein, the role of which has not been fully elucidated; however, it appears to function as a tumor suppressor. Studies have found that folliculin interacts with FLCN-interacting protein 1 and is involved in 5′-AMP activated protein kinase and mTOR signaling dysregulation.3

Renal tumors and spontaneous pneumothoraces are strongly linked to BHDS. There is a 50-fold increased risk of spontaneous pneumothorax, and recurrent disease is common. Pneumothorax is probably related to the presence of multiple lung cysts, which have been reported in more than 80% of adult patients and are typically found at the lung bases.4

Patients with BHDS have a 16% risk of developing renal cell carcinoma by age 70 years, which is often bilateral and multifocal.5 Chromophobe renal carcinoma and oncocytomas are most commonly reported. Although there is no consensus on screening guidelines, renal magnetic resonance imaging surveillance beginning at age 20 years has been recommended.1

Treatment for the cutaneous manifestations of BHDS is difficult. Multiple modalities, including ablative lasers, electrodessication, and surgical excision have been reported. While surgical excision is the only definitive treatment for individual lesions, the scarring risk makes this an unreasonable option for multiple lesions. A recent double-blind placebo-controlled randomized trial using topical rapamycin yielded disappointing results.6 Most importantly, appropriate imaging studies for renal tumors and lung cysts should be obtained in all patients with BHDS as well as at-risk relatives.

To our knowledge, this patient is the first reported case of BHDS in an individual of African ancestry and is associated with an FLCN gene mutation that has not been previously described.

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Article Information

Corresponding Author: Ellen N. Pritchett, MD, MPH, Department of Dermatology, Drexel University College of Medicine, 219 N Broad St, Fourth Floor, Philadelphia, PA 19107 (

Published Online: November 19, 2014. doi:10.1001/jamadermatol.2014.3720.

Conflict of Interest Disclosures: None reported.

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