Birt–Hogg–Dubé Syndrome: An Update

Abstract Birt–Hogg–Dube syndrome is a rare autosomal dominant genodermatosis that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The most common histological types found in renal tumors from patients with the syndrome are oncocytoma–chromophobe carcinoma hybrids and pure forms of chromophobe carcinoma, oncocytic carcinoma, and clear cell or papillary cell carcinoma. The syndrome is linked to mutations in the FLCN gene, which encodes folliculin and is preferentially expressed in the skin, kidney, and lung. The syndrome can exhibit a high degree of clinical variability, and the skin lesions that are a warning sign for dermatologists may be absent in up to 70% of cases. Consequently, although skin lesions and mutations in FLCN are the main diagnostic criteria for Birt–Hogg–Dube syndrome, a diagnosis can be made based on noncutaneous manifestations, with or without known family history of the syndrome, even in the absence of histological confirmation of fibrofolliculomas or trichodiscomas.