The phenotypic features of the Birt-Hogg-Dubé syndrome (BHD) are benign tumors of the hair follicle (fibrofolliculomas), spontaneous pneumothorax, and an increased risk for developing renal tumors. The BHD syndrome is inherited in an autosomal dominant pattern. Fibrofolliculomas are pilar hamartomas characterized by proliferation of both epithelial and fibrous tissue.
BHD patients are predisposed to develop renal carcinomas. Renal tumors may be solitary or multiple and bilateral. All histologic types of renal carcinoma occur in BHD patients. The most common type found in association with the BHD syndrome is a hybrid neoplasm with features of both renal oncocytoma and chromophobe renal carcinoma.
The BHD gene, located at chromosome 17p11.2, encodes a novel protein that has no known homology to other human proteins but is conserved across species. BHD is widely expressed in multiple tissues, and alternative transcripts have been reported.
Nearly half the germline mutations identified to date occur as a cytosine insertion or deletion in a hypermutable C8 tract within exon 11 of the BHD gene. Most germline mutations in the BHD gene are predicted to truncate the BHD protein, folliculin, suggesting a role as a tumor suppressor.