his lungs and kidneys. Hornstein-Knickenberg syndrome is a now-deprecated name for the inherited fibrofolliculomas inherent to BHD. Birt, Hogg, and Dubé examined a family with a hereditary thyroid cancer, and discovered that many of the members had fibrofolliculomas, trichodiscomas, and acrochordons, which became defined as the classical symptoms of the eponymous disease. The first case of spontaneous pneumothorax associated with BHD was discovered in 1986; the first case of renal cancer followed in 1993, and the presence of lung cysts in people with BHD was confirmed in 1999. People with BHD were once thought to be at higher risk for colorectal polyps and neoplasms, but this has been disproven. The BHD Foundation supports research into the syndrome and holds regular symposia in BHD and related disorders for researchers, clinicians, and family members. Other animals Genes related to FLCN and diseases similar to BHD have been found in dogs, fruit flies, rats, and mice. In German Shepherd dogs, missense mutations in the canine ortholog of FLCN cause a similar phenotype to human BHD—kidney cancers (in this case, multifocal renal cystadenocarcinoma) and skin tumors (nodular dermatofibrosis). They had a similar pattern of tumorigenesis to human BHD in that the skin lesions were heterozygous for the FLCN mutation, and the renal tumors were likely caused by loss of heterozygosity. Female German Shepherds with a FLCN mutation are also prone to uterine leiomyomas. A homolog of FLCN called DBHD has been discovered in the common fruit fly, Drosophila melanogaster. Decrease expression of the DBHD results in loss of male germline stem cells (GSC), which suggest that DBHD is required for male GSC maintenance in the fly testis. Further, DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways, which suggest that BHD regulates tumorigenesis by controlling stem cells in human { Singh et al. 2006} A line of rats with hereditary kidney cancer were developed by Japanese researchers. They have a mutation in the FLCN homolog that produces a truncated protein, though they do not develop the cutaneous or pulmonary symptoms seen in humans. Heterozygotes have renal abnormalities seen very early in life that develop into clear-cell and hybrid tumors, significantly shortening the animals' lifespans; they also are prone to endometrial and salivary gland clear-cell hyperplasia as well as rhabdomyolysis. Homozygotes do not survive to birth. When a wild-type FLCN gene was added, the phenotype was rescued. Knockout mice