a permanent solution, though, as the tumors often recur. Dermatologic examination every 6-12 months due to risk of melanoma . Thyroid/parotid ultrasound should be considered annually. Colonoscopies should be considered. The renal and pulmonary symptoms are managed preventatively: CT scans, ultrasounds, or MRIs of the kidneys are recommended regularly, and family members are advised not to smoke. MRIs are the preferred method for surveillance of the kidneys in people with BHD because they do not carry the same risk of radiation complications as CT scans, and are more sensitive than ultrasounds. Smokers with Birt–Hogg–Dubé have more severe pulmonary symptoms than non-smokers. Though nephrectomy is sometimes indicated, kidney tumors in cases of BHD are often removed without taking the whole kidney, in a partial nephrectomy. Knockout mouse studies have shown that administration of rapamycin may mitigate the effects of FLCN mutations on kidneys and improve renal cancer prognoses because of folliculin's interaction with the mTOR pathway. Epidemiology The disorder has been reported in more than 100 families worldwide, though some sources cite up to 400 families, and it is inherited in an autosomal dominant pattern. It is considered to be under-diagnosed because of the variability in its expression. The pattern of mutations and spectrum of symptoms are heterogeneous between individuals. Less severe skin phenotypes are seen in women and people of both sexes who have a late onset of skin symptoms. Patient registry Birt-Hogg-Dubé Syndrome patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy-protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases. History The syndrome was first well described in 1977, by three Canadian physicians, Arthur R. Birt, Georgina R. Hogg, and William J. Dubé. The earliest case of possible BHD in the medical literature was published by Burnier and Rejsek in 1927, who described a case of perifollicular fibromas on a 56-year-old woman's face. Trichodiscomas were first described in 1974 by H. S. Zackheim and H. Pinkus, but were not associated with BHD until Birt, Hogg, and Dubé. The first case of BHD with the systemic symptoms was described by Hornstein and Knickenberg and found in two siblings and their father, all of whom exhibited colon polyps and the characteristic fibrofolliculomas. Though the siblings did not have renal or pulmonary symptoms, their father had cysts in