A40-19 From Collapsed Lungs to Renal Tumors: The Evolving Spectrum of Birt-Hogg-Dubé Syndrome

Abstract Introduction Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant condition caused by germline mutations in the FLCN tumor suppressor gene. The loss of function of FLCN gene results in aberrant cell proliferation and cyst formation. BHD classically presents with a triad of pulmonary cysts and recurrent pneumothoraces, cutaneous fibrofolliculomas, and renal tumors. The manifestations are age-dependent; pulmonary findings often appear before age 30, skin lesions typically emerge in the 30s to 40s, and renal involvement tends to occur later in life. Because of this staggered presentation and wide phenotypic variability, BHD is frequently underrecognized. We present two patients with BHD syndrome, each demonstrating distinct phenotypic severity. Cases A 22-year-old man presented with sudden-onset, non-radiating central chest pain that worsened with exertion. Physical examination revealed decreased breath sounds over the left upper and lower lung fields. Chest X-ray demonstrated a large left-sided pneumothorax, which resolved following emergent chest tube placement. High-resolution CT of the chest showed numerous small, thin-walled cysts bilaterally with mild subpleural involvement, consistent with BHD syndrome. His family history was notable for the disease in his father and grandfather. Genetic testing confirmed a pathogenic variant in the FLCN gene (c.1285dupC). He was counselled on the risk of recurrence, advised to avoid high-pressure activities such as air travel without medical clearance, and referred for renal imaging surveillance.A 57-year-old woman with genetically confirmed BHD has experienced multiple spontaneous, recurrent pneumothoraces, requiring pleurodesis and partial lung resection. Chest CT shows numerous bilateral pulmonary cysts, and recent renal imaging revealed a newly developed 2.3 cm mixed-density lobulated mass in the left kidney. She reports progressive dyspnea and requires nocturnal oxygen supplementation. Discussion This case report highlights the wide phenotypic variability and the progressive nature of BHD syndrome. The syndrome demonstrates pleiotropy with variable penetrance and severity across pulmonary, cutaneous, and renal systems. Because early presentations often involve nonspecific pulmonary findings, clinicians should maintain a high index of suspicion when evaluating patients, particularly those with a personal or family history of pneumothorax. Comprehensive assessment and timely recognition are essential for accurately diagnosing and treating this underrecognized hereditary disorder. Conclusion These cases emphasize the need for clinician awareness of BHD’s variable presentations to prevent missed or delayed diagnoses. Early genetic testing and family screening are key steps toward reducing complications. Greater inclusion of BHD in cystic lung disease registries may improve understanding of its natural history and inform standardized surveillance protocols. This abstract is funded by: none