Abstract Rationale Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by pathogenic variants in the FLCN gene, characterized by fibrofolliculomas, pulmonary cysts predisposing to spontaneous pneumothorax, and an increased risk of renal neoplasms. Despite its multisystem implications, BHD remains under-recognized, particularly in respiratory practice, where recurrent pneumothorax is often attributed to more common aetiologies. Early identification allows targeted surveillance and treatment of renal cancer and recurrent pneumothorax. We present clinical and radiologic findings from three families with confirmed BHD to illustrate its phenotypic spectrum and the need for multidisciplinary recognition. Methods A retrospective review was conducted of three families with confirmed FLCN mutations followed at our institution. Genetic screening is complete in one family, partially complete in the second and screening is ongoing in the third. Pedigrees were constructed to assess inheritance patterns. A full clinical analysis was undertaken including the presence of pulmonary, renal and dermatological manifestations. Serial CT images of the thorax were reviewed to assess cyst distribution and morphology. Serial pulmonary function tests (PFTs) were analyzed including lung volumes and DLCO where available. Family members were screened for renal lesions by MRI. In addition routine bloods and biomarkers were sampled on all confirmed BHD cases. Descriptive analysis was performed to identify shared and divergent features across families. Results In total, 20 individuals across the three pedigrees have been diagnosed with BHD, with additional diagnoses anticipated as ongoing screening and clinical assessments continue. Spirometry was largely preserved throughout the cohort. However, considerable variability was observed in clinical presentation, even among genetically related individuals. High-resolution CT imaging consistently demonstrated multiple, bilateral, thin-walled pulmonary cysts, with heterogeneity in cyst size and number. Dermatologic fibrofolliculomas were subtle and frequently under-recognized. Pedigree analysis revealed incomplete penetrance and marked phenotypic variability both within and between families. Conclusion BHD remains an underdiagnosed cause of familial or recurrent spontaneous pneumothorax. Recognition of characteristic cystic lung changes on imaging, especially in patients with a relevant family history, should prompt FLCN testing and renal surveillance. Multidisciplinary collaboration among pulmonologists, geneticists, and nephrologists is essential for early diagnosis and cancer treatment. Increasing awareness of BHD in respiratory medicine is critical to improving outcomes through timely recognition and management. This abstract is funded by: None
Mulpeter et al. (Fri,) studied this question.
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