Familial Birt-Hogg-Dubé syndrome diagnosed with the rare FLCN exon 6 variant: a case series of three related patients

Birt-Hogg-Dubé Syndrome (BHDS) is a rare, autosomal dominant genodermatosis characterized by a triad of benign cutaneous lesions, pulmonary cysts or spontaneous pneumothorax, and renal tumors. The clinical presentation is heterogeneous and often underrecognized, leading to diagnostic delays. We present a case series of three genetically related individuals diagnosed with BHDS. All patients demonstrated characteristic dermatological findings, including multiple fibrofolliculoma-like lesions on the face and trunk. Pulmonary involvement varied: one case was incidentally detected on imaging, while two patients presented with spontaneous pneumothorax requiring surgical intervention. Renal involvement ranged from benign renal cysts to a history of nephrectomy for oncocytoma. Genetic testing confirmed the FLCN variant in Case 3; Cases 1 and 2 were diagnosed clinically based on typical findings and family history. This case series highlights the broad clinical spectrum of BHDS and underscores the importance of clinician and radiologist awareness to facilitate early diagnosis. Multidisciplinary management and screening of first-degree relatives are critical to prevent morbidity and mortality associated with renal tumors and pneumothorax.