Elena Torricelli1, Mariaelena Occhipinti2, Edoardo Cavigli3, Giorgia Tancredi4, Elisabetta Rosi2, Cesare Rossi5, Michela Bonaguro5, Luisa Candita6, Laura Papi6, Luca Novelli7, Michela Bezzi8, Elena Bargagli2, Luca Voltolini4, Massimo Pistolesi2. 1. Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy, elenatorricelli83@gmail.com. 2. Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. 3. Section of Radiodiagnostics, Department of Services, Careggi University Hospital, Florence, Italy. 4. Section of Thoracic Surgery, Department of Surgery, University of Florence, Florence, Italy. 5. Section of Medical Genetics, Sant'Orsola-Malpighi Hospital, Bologna, Italy. 6. Section of Medical Genetics, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy. 7. Section of Histopathology and Molecular Pathology, University of Florence, Florence, Italy. 8. Division of Interventional Pulmonology, Careggi University Hospital, Florence, Italy.
Abstract
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disorder characterized by inactivation of the gene Folliculin (FLCN), pulmonary cysts with recurrent spontaneous pneumothorax, dermatological lesions, and an increased risk of developing renal malignancies. OBJECTIVES: We aimed to investigate the real prevalence of BHDS and its prevalence among patients with a familial history of pneumothorax. METHODS: From July 2014 to December 2016, we consecutively studied all patients with spontaneous pneumothorax and a positive family history for the same condition referring to our Institution. The suspicious cases underwent genetic analysis of the BHDS-causative gene FLCN. FLCN-positive cases were further evaluated with routine blood tests, chest radiography, chest CT, abdominal MRI, and dermatological evaluation. RESULTS: Among 114 patients admitted with spontaneous pneumothorax, 7 patients had a family history of pneumothorax, and 6/7 (85.7%) patients had positive genetic test for FLCN as well as 7/13 family members. Pulmonary cysts were found in all patients with a FLCN-positive genetic test. Most patients (10/13, 76.9%) had tiny pulmonary cysts less than 1 cm in diameter. The vast majority of cysts were intraparenchymal (12/13, 92.3%) and located in lower lobes. Dermatological lesions were found in 7/13 (54%) patients, renal cysts in 4/13 (31%) patients, and renal cancer in 1 (1/13, 7.7%) patient. CONCLUSIONS: Although BHDS is considered a rare disease, BHDS underlies spontaneous pneumothorax more often than usually believed, especially whenever a family history of pneumothorax is present. Diagnosis of BHDS is essential to start monitoring patients for the risk of developing renal malignancies.
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disorder characterized by inactivation of the gene Folliculin (FLCN), pulmonary cysts with recurrent spontaneous pneumothorax, dermatological lesions, and an increased risk of developing renal malignancies. OBJECTIVES: We aimed to investigate the real prevalence of BHDS and its prevalence among patients with a familial history of pneumothorax. METHODS: From July 2014 to December 2016, we consecutively studied all patients with spontaneous pneumothorax and a positive family history for the same condition referring to our Institution. The suspicious cases underwent genetic analysis of the BHDS-causative gene FLCN. FLCN-positive cases were further evaluated with routine blood tests, chest radiography, chest CT, abdominal MRI, and dermatological evaluation. RESULTS: Among 114 patients admitted with spontaneous pneumothorax, 7 patients had a family history of pneumothorax, and 6/7 (85.7%) patients had positive genetic test for FLCN as well as 7/13 family members. Pulmonary cysts were found in all patients with a FLCN-positive genetic test. Most patients (10/13, 76.9%) had tiny pulmonary cysts less than 1 cm in diameter. The vast majority of cysts were intraparenchymal (12/13, 92.3%) and located in lower lobes. Dermatological lesions were found in 7/13 (54%) patients, renal cysts in 4/13 (31%) patients, and renal cancer in 1 (1/13, 7.7%) patient. CONCLUSIONS: Although BHDS is considered a rare disease, BHDS underlies spontaneous pneumothorax more often than usually believed, especially whenever a family history of pneumothorax is present. Diagnosis of BHDS is essential to start monitoring patients for the risk of developing renal malignancies.
Authors: Jincey D Sriram; Irma van de Beek; Paul C Johannesma; Michiel H van Werkum; Tijmen J W T van der Wel; Elise M Wessels; Hans J J P Gille; Arjan C Houweling; Pieter E Postmus; Hans J M Smit Journal: BMC Pulm Med Date: 2022-08-26 Impact factor: 3.320