Familial spontaneous pneumothorax: importance of screening for Birt–Hogg–Dubé syndrome

OBJECTIVES: The goal of this study was to investigate the prevalence of Birt-Hogg-Dube (BHD) syndrome in patients with familial spontaneous pneumothorax (FSP) and the clinical characteristics of pneumothorax related to BHD syndrome compared with those of primary spontaneous pneumothorax. METHODS: A total of 37 families diagnosed with FSP from 2007 to 2017 were enrolled in this study. The FLCN gene, which is responsible for BHD syndrome, was sequenced using the Sanger method in 25 probands. For the patients with confirmed BHD syndrome-related pneumothorax, clinical characteristics including the median onset age of pneumothorax, the male-to-female ratio, the mean height and body mass index (BMI) and the recurrence rate after different treatment modalities were obtained and compared with those of patients with primary spontaneous pneumothorax. RESULTS: Of the 25 probands with FSP, 16 [64.0%, 95% confidence interval (CI) 43.8-84.2%] harboured FLCN germline mutations. In the patients with BHD syndrome-related pneumothorax, the median onset age of pneumothorax was 34 years; the male-to-female ratio was 1.3:1; and the mean height and BMI were 167.0 +/- 8.6 cm and 23.6 +/- 3.4 kg/m2, respectively. These characteristics were significantly different from those in patients with primary spontaneous pneumothorax from the same centre. The recurrence rate of BHD syndrome-related pneumothorax after conservative therapy was 53.1% (95% CI 38.6-67.5%) compared with 9.1% (95% CI 0-19.4%) after surgical treatment. CONCLUSIONS: BHD syndrome is one of the most common causes of FSP. Patients with FSP should be recommended for mutation screening for the FLCN gene to facilitate early diagnosis and proper intervention.