Focus on the pulmonary involvement and genetic patterns in Birt-Hogg-Dube syndrome: Literature review

Introduction: Brit-Hogg-Dube syndrome (BHD) is a rare disorder that is estimated to affects about 600 families inthe World. The disease-causing mutations is on FLCN gene which codes for folliculin. This protein has a role indifferent organs as skin, kidney and lung, thanks to the interaction with type I and II cadherins, RhoA activity andthe regulation of AMPK, mTORC1 pathways and cell adhesion.The aim of our study is to focus on the manifestation of the syndrome, especially the pulmonary involvement,then on genetical analysis and on the available treatments.Material and methods: We collected 15 previous studies where we found medical history information, clinicalmanifestations, radiological and histological diagnosis and genetical analysis.Results: The prevalence of pneumothorax in patients with BHD syndrome was about 65%, but the lunginvolvement with multiple small cysts, localized especially in the lower part, was 85%. The prevalence of renalinvolvement in BHD patients ranged from 6.5% to 34%, while skin lesions ranged from 11% to 50%. More than150 FLCN germline has been described, though the mutation in exon 11 is the most frequently detected, especiallyamong Caucasian population.Conclusions: BHD syndrome is rare and usually the first manifestations appear in early age. In patients with theseclinical and radiological characteristics we suggest taking a careful medical history, though the diagnosis of BHDsyndrome should be confirmed with the analysis of FLCN gene