Pathogenic variants (disease-causing) in the FLCN gene are associated with Birt–Hogg–Dubé syndrome. This condition predisposes individuals to fibrofolliculomas (benign skin tumors), pulmonary cysts with risk of spontaneous pneumothorax (collapsed lung), and an increased risk of kidney cancer, particularly chromophobe and hybrid oncocytic tumors. The syndrome is variable, and not all affected individuals develop all features. Management of FLCN–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. FLCN variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in FLCN exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
Resources:
Birt-Hogg-Dubé Syndrome Foundation
Written December 2025
