Abstract Introduction Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disorder caused by pathogenic variants in the FLCN gene, which encodes folliculin. It is characterised by fibrofolliculomas, pulmonary cysts with predisposition to spontaneous pneumothorax, and an increased risk of renal neoplasia, particularly chromophobe renal cell carcinoma and hybrid oncocytic tumours. Over 600 families with BHDS have been described worldwide, though diagnosis is often delayed due to variable presentation. Pulmonary manifestations may precede cutaneous or renal findings, placing respiratory physicians in a critical role. We report a case of BHDS initially presenting with spontaneous pneumothorax. Case Presentation A 48-year-old male with asthma and keratoconus presented with sudden left apical chest pain and dyspnea in January 2023. He denied trauma, hemoptysis, fever, or travel. Examination showed hemodynamic stability with mild left parascapular discomfort. Chest radiograph revealed a 3.7 cm left apical pneumothorax, which enlarged to 5.3 cm, requiring chest drain insertion. Blood tests were unremarkable. Follow-up HRCT demonstrated multiple thin-walled pulmonary cysts, including a 23 × 17 mm subpleural cyst in the left upper lobe. At clinic review, multiple papular lesions on the nose and cheeks were noted, consistent with fibrofolliculomas. Dermatology referral was arranged. The combination of cystic lung disease, pneumothorax, and fibrofolliculomas raised suspicion of BHDS. Genetic testing confirmed a heterozygous FLCN frameshift variant. The patient was referred to genetics for counselling and cascade testing. His father had similar facial lesions but no history of pneumothorax or renal disease. Renal surveillance with CT (October 2023) and MRI (August 2024) showed no renal masses or cysts. Discussion BHDS is a multisystem disorder first described in 1977, caused by FLCN pathogenic variants. Pulmonary cysts occur in 80% of patients, typically bilateral and subpleural, with pneumothorax in 30-40%. Fibrofolliculomas are a diagnostic clue but may be subtle. Renal malignancy risk is estimated at 15-30%, often bilateral and multifocal. In this case, subtle dermatological findings were key to diagnosis. Surveillance with MRI every 1-2 years is recommended from age 20, even if baseline imaging is normal, to detect renal tumours early. Recognition of syndromic causes of pneumothorax is essential, as diagnosis carries implications for patient management and family screening. Conclusion BHDS should be considered in patients with spontaneous pneumothorax, particularly in non-smokers with pulmonary cysts and subtle skin lesions. Early recognition enables renal surveillance, genetic counselling, and family testing, improving outcomes through timely diagnosis and multidisciplinary care. This abstract is funded by: self
Alshabatat et al. (2026) studied this question.