Birt-Hogg-Dube: A syndrome the geneticist should know. C.D. DeLozier^{1, 2}, T. Treisman¹, Y. Chang³, D. Tashjian⁴, T. McCalmont⁵, C.J. Curry⁶. 1) Genetic Medicine, Central California Faculty Medical Group, Fresno, CA; 2) Genetics Department, Kaiser Permanente Fresno, CA; 3) Urology Department, Kaiser Permanente Fresno, CA; 4) Dermatology Associates, Fresno, CA; 5) Dermatopathology, University of California San Francisco, CA; 6) Department of Pediatrics, UCSF-Fresno Medical Education Program Fresno, CA.
   In our full-service genetics consultation we see approximately 200 families/year for assessment of a hereditary predisposition to cancer. Most consultations concern breast/ovarian or colorectal cancers, and most gene testing comes back negative. Although textbooks suggests that rare cancer-predisposition syndromes account for less than one percent of familial aggregation of cancer, our experience suggests that syndromic entities may well be under-diagnosed. One such condition is the Birt-Hogg-Dube (BHD) syndrome, due to mutations in the presumed tumor-suppressor gene folliculin (FCN) on chromosome 17p. BHD is best known to dermatologists because of skin lesions with characteristic histology: fibrofolliculomas, trichodiscomas and acrochordons. Renal tumors, specifically oncocytomas and oncocytic hybrid tumors with both malignant and benign lesions, occur in approximately 30% of BHD patients. The gene mutation also predisposes to spontaneous pneumothorax/pulmonic cysts and to benign and malignant tumors of the uterus, ovaries, breast and colon. We describe here the clinical, genetic and histological features of three families with BHD syndrome presenting to the cancer genetics consultation in the same year. All adults over 30 had typical facial and thoracic skin lesions and each family had at least one person with a benign or malignant kidney tumor. Two families had pneumothorax. A fourth proband presented with primary spontaneous pneumothorax, had no other clinical features at the age of 46. We believe that a thorough physical exam and the conscientious histological verification of benign and malignant tumors in individuals attending the cancer genetics clinic will result in improved detection and management of this under-diagnosed cancer predisposition syndrome.