Birt–Hogg–Dubé syndrome
Open Access
- 17 September 2020
- journal article
- research article
- Published by European Respiratory Society (ERS) in European Respiratory Review
- Vol. 29 (157), 200042
- https://doi.org/10.1183/16000617.0042-2020
Abstract
Birt–Hogg–Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.Keywords
This publication has 137 references indexed in Scilit:
- Renal cancer and pneumothorax risk in Birt–Hogg–Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD familiesBritish Journal of Cancer, 2011
- Identification of intragenic deletions and duplication in the FLCN gene in Birt‐Hogg‐Dubé syndromeGenes, Chromosomes and Cancer, 2011
- Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signalingMolecular Cancer, 2010
- Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting featureJournal of Medical Genetics, 2010
- The role of the Birt–Hogg–Dubé protein in mTOR activation and renal tumorigenesisOncogene, 2009
- BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reportsJournal of Medical Genetics, 2008
- Lung Cysts, Spontaneous Pneumothorax, and Genetic Associations in 89 Families with Birt-Hogg-Dubé SyndromeAmerican Journal of Respiratory and Critical Care Medicine, 2007
- Mutations of the Birt Hogg Dube gene in patients with multiple lung cysts and recurrent pneumothoraxJournal of Medical Genetics, 2007
- Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signalingProceedings of the National Academy of Sciences of the United States of America, 2006
- Mutation and Cancer: Statistical Study of RetinoblastomaProceedings of the National Academy of Sciences of the United States of America, 1971