Two genetically confirmed Japanese cases of Birt–Hogg–Dubé syndrome presenting with pneumothorax, including early-onset bilateral renal tumors in one case

Abstract Background: Birt Hogg Dube (BHD) syndrome is an autosomal dominant disorder caused by pathogenic variants in FLCN . It characteristically features multiple pulmonary cysts and spontaneous pneumothorax, renal tumors, and cutaneous fibrofolliculomas, with renal tumors most often diagnosed in middle age [1–3] . Case presentation: We report two genetically confirmed Japanese patients with contrasting BHD phenotypes. Case 1 was a 25-year-old woman with recurrent bilateral pneumothorax and basally predominant subpleural cysts; sequencing identified an FLCN splice variant (c.1062+1G>A). Abdominal imaging showed no renal lesions, and she remains under surveillance. Case 2 was a 29-year-old man with right pneumothorax, multiple facial papules consistent with fibrofolliculomas, and bilateral renal tumors; genetic testing detected the recurrent frameshift variant FLCN c.1285dupC (exon 11). He underwent bilateral nephron-sparing surgery, and pathology revealed hybrid oncocytic/chromophobe tumors. Conclusions: These cases illustrate the phenotypic spectrum of BHD in young adults and support early FLCN testing in recurrent pneumothorax to enable risk-adapted renal surveillance and timely nephron-sparing management [1–3,6] . Only one patient developed early-onset bilateral renal tumors (Case 2).