A46-27 One Patient, Three Diagnoses: Familial Birt-Hogg-Dubé Syndrome Revealed Through Recurrent Pneumothoraces

Abstract Introduction Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant disorder caused by pathogenic variants in the FLCN gene encoding folliculin. It is characterized by cutaneous fibrofolliculomas, pulmonary cysts with a high risk of recurrent spontaneous pneumothoraces, and renal neoplasms. Diagnosis is often delayed until repeated pulmonary events or incidental skin findings prompt genetic evaluation. Recognition of an index case is crucial, as cascade testing can identify affected relatives and enable early surveillance to prevent complications. Case Presentation A 32-year-old woman with asthma was evaluated for dyspnea and chest pain multiple times. In January 2017, she was diagnosed with a left pneumothorax managed with chest-tube placement. One month later, she experienced a recurrence requiring repeat chest tube insertion and VATS with blebectomy. In 2018, she presented with a right pneumothorax treated with tube thoracostomy. Three years later, in 2021, she developed another right pneumothorax requiring chest-tube placement followed by right-sided VATS blebectomy and pleurodesis for recurrence prevention. A dermatologic evaluation revealed multiple facial papules consistent with fibrofolliculomas, prompting further investigation. High-resolution CT (HRCT) of the chest demonstrated numerous thin-walled, lower-lobe-predominant cysts, while CT of the abdomen and pelvis showed no renal lesions. Genetic testing confirmed a pathogenic FLCN mutation, establishing the diagnosis of BHDS. Cascade genetic testing identified her father and paternal aunt as carriers; her father had two prior spontaneous pneumothoraces, and her aunt had undergone partial nephrectomy for a renal tumor ten years earlier, demonstrating variable phenotypic expression within the family. At follow-up, the patient remained clinically stable with preserved pulmonary function and no new respiratory symptoms. She was counseled to avoid smoking, scuba diving, and unpressurized flight and was enrolled in a renal surveillance protocol using MRI every three years to limit radiation exposure. Discussion BHDS should be suspected in patients with recurrent spontaneous pneumothoraces and characteristic lower-lobe cystic changes on HRCT, even when spirometry is normal. Pulmonary involvement arises from cyst rupture rather than progressive fibrosis. Systemic immunosuppression has no therapeutic role. Early recognition allows for family screening, genetic counseling, and renal tumor surveillance, all of which reduce long-term morbidity. Conclusion This case highlights how recurrent bilateral pneumothoraces in a young, otherwise healthy woman led to the diagnosis of BHDS, uncovering the condition in multiple family members. Recognizing this clinical pattern should prompt multidisciplinary evaluation and genetic testing to identify at-risk relatives. Early diagnosis guides preventive pulmonary management and lifelong renal surveillance, mitigating recurrence and malignancy risk. This abstract is funded by: None