An Underrecognized Cause of Recurrent Spontaneous Pneumothorax: Birt-Hogg-Dubé Syndrome With Isolated Pulmonary Manifestation.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder characterized by a classic triad of cutaneous fibrofolliculomas, bilateral pulmonary cysts and renal tumours. Pulmonary manifestations may occur in isolation, posing a significant diagnostic challenge. We report a 50-year-old non-smoking woman with recurrent pneumothorax referred to our pulmonology clinic for dyspnoea on exertion. Chest CT revealed multiple bilateral pulmonary cysts with lower-lobe predominance. Review of prior wedge resection specimens showed subpleural and parenchymal cysts lined by flattened epithelium. Negative immunohistochemical staining for HMB-45 and GPNMB excluded lymphangioleiomyomatosis. Given the characteristic cyst pattern, germline whole-exome sequencing identified a pathogenic heterozygous FLCN frameshift variant, confirming the diagnosis. Because of the lifetime risk of renal malignancy, early recognition is important and genetic testing is recommended when BHD is suspected.