Birt-Hogg-Dubé Syndrome: A Large Single Family Cohort

Kate Skolnik; Willis H. Tsai; Kimberly Dornan; Renée Perrier; Paul W. Burrowes; Warren J. Davidson


Respiratory Research. 2016;17(22) 

In This Article


Birt-Hogg- Dubé (BHD) syndrome is a rare autosomal dominant condition characterized by skin lesions, pulmonary cysts, spontaneous pneumothoraces, and renal tumors.[1]

It was first described as an inherited dermatologic syndrome in the 1970s, however future studies identified pulmonary and renal manifestations as key features of the disease.[2] The gene responsible for the syndrome, FLCN, was mapped to chromosome 17p12q11.2[3] and cloned in 2002.[4] The product, folliculin, is found in many normal tissues and thought to play a role in tumor suppression.[4] There are over 70 unique pathogenic FLCN gene mutations.[5]

BHD dermatologic lesions are common and include fibrofolliculomas (face, trunk, and arm papules), trichodiscomas, and acrochordons (skin tags).[6] Renal cysts and tumors (including chromophobe renal cell carcinoma) are frequently seen and are often multiple and bilateral.[7] Lung cysts are also common and the age-adjusted risk of pneumothorax has been estimated as high as 50.3.[8,9]

Only 430 families worldwide have been documented with BHD Syndrome,[10,11] with the largest reporting twenty-five affected members.[12] We present findings from the largest single family cohort described to date. The primary objective of the case series was to characterize the cystic lung changes on computed tomography (CT) chest scanning and identify features that stratify patients at higher risk of pneumothorax. The secondary objectives included: (1) description of the type and natural history of BHD-associated pneumothorax; (2) pulmonary function characteristics; and (3) influence of the degree of cystic lung changes on pulmonary function.