Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer

Background: * Birt-Hogg-Dube (BHD) is a rare, autosomal dominantly inherited disorder which confers susceptibility to develop multifocal, bilateral renal cancer, spontaneous pneumothorax and fibrofolliculomas. * BHD is caused by mutations in the FLCN gene located on Chromosome17p11.2 * Defining the genetic and biochemical pathways leading to renal tumorigenesis in BHD may lead to the development of new molecularly targeted drugs. Objectives: * To define the types and characteristics (including patterns of growth) of renal cancer associated with BHD * To determine the risk of renal cancer, lung cysts and fibrofolliculomas in individuals with BHD * To define the natural history of BHD related renal tumors * To determine if other genes contribute to BHD * Identify genotype/phenotype correlations Eligibility: -Individuals that meet one or more of the following criteria: --Suspected or known to have phenotype or genotype suggestive of Birt-Hogg-Dube (BHD), such as: * Individuals with histologically confirmed fibrofolliculomas * Individuals with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and/or a family history of spontaneous pneumothorax or kidney cancer * Individuals with a known germline FLCN mutation or --Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, hybrid oncocytic neoplasm or oncocytoma or --Are a relative (related by blood) of an individual with a confirmed or suspected diagnosis of BHD Design: * These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors. * Genetic testing will be offered to gain appreciation of the effect of mutations the BHD gene and to assess the relative activity of various germline and somatic mutations. * We will determine if there is a relationship between mutation and disease manifestations and phenotype.