Abstract
RATIONALE: Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant disorder characterized by a triad of manifestations, including recurrent spontaneous pneumothorax, multiple cutaneous fibrofolliculomas, and renal neoplasms. Familial clustering of spontaneous pneumothorax should raise clinical suspicion of BHD syndrome. This syndrome is caused by pathogenic variants of the folliculin gene (FLCN gene) encoding folliculin, which predisposes to pneumothorax through dysregulated matrix metalloproteinase activity, leading to elastic fiber degradation in the pulmonary parenchyma. PATIENT CONCERNS: A 28-year-old female presented with recurrent pneumothorax and a family history of primary spontaneous pneumothorax. Emergency video-assisted thoracoscopic surgery with bullectomy and cyst resection was performed. DIAGNOSES: The FLCN gene mutation was confirmed by genetic testing after surgery. The clinicopathological characteristics, molecular genetics, and therapeutic strategies for BHD syndrome have been discussed in the literature. The female who experienced 3 episodes of spontaneous pneumothorax within 24 months. Notably, her multigenerational family history included her paternal uncle and cousins affected by primary spontaneous pneumothorax. INTERVENTIONS: Emergency video-assisted thoracoscopic surgery revealed multiple subpleural cysts (3-15 mm in diameter), predominantly in the lower lung lobes, requiring bullectomy and cyst wall resection. Histopathological analysis revealed characteristic thin-walled cysts lined with alveolar epithelium. Postoperative genetic sequencing revealed a heterozygous splice-site variant in FLCN gene, establishing a diagnosis of BHD syndrome. OUTCOMES: After regular follow-up, the patient had no recurrence of spontaneous pneumothorax, such as bullae rupture, until recently. This case highlights the importance of integrating radiological findings with molecular diagnostics for the evaluation of recurrent pneumothorax. It is particularly necessary to emphasize that the patient and her legal guardian has given us informed consent. Chengdu-Shangjin Nanfu Hospital ethics Committee has approved this study. LESSONS: This case shows a typical phenomenon of family clustering that should raise clinical suspicion of BHD syndrome. BHD syndrome is a rare autosomal dominant genetic disorder that caused by mutations in FLCN gene. The gene is a tumor suppressor gene that encodes the follicle-stimulating hormone folliculin. Follicle-stimulating hormone folliculin is expressed in most tissues, including the skin and its appendages, type I alveolar epithelial cells, and distal renal tubular epithelial cells, which explains why BHD syndrome occurs in the skin, lungs, and kidneys. The literature review shows that there are 12 similar cases, including the male-to-female ratio and average age. Thoracoscopic surgery had the best effect, followed by conservative treatment, and the recurrence rate was higher after closed thoracic drainage. Due to the rarity of this syndrome, this article reminds clinicians to pay attention to its familial clustering characteristics during diagnosis and treatment, and also reminds other family members to pay attention to screening for the clinical features related to this syndrome, so as to facilitate early treatment. Furthermore, this case also provides significant reference value for identifying the causes and molecular mechanisms of spontaneous pneumothorax, especially those with a familial clustering tendency.