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

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant disorder caused by pathogenic variants in FLCN and associated with pulmonary cysts with recurrent pneumothorax, renal tumors, and cutaneous fibrofolliculomas. Renal neoplasms usually arise in midlife; occurrence in the third decade is uncommon (Menko et al. in Lancet Oncol 10:1199–1206, 2009; Toro et al. in Arch Dermatol 135:1195–1202, 1999; Zbar et al. in Cancer Epidemiol Biomarkers Prev 11:393–400, 2002). We describe two genetically confirmed Japanese patients. Case 1 was a 25-year-old woman with recurrent bilateral pneumothorax and basally predominant subpleural cysts; sequencing identified an FLCN splice-site variant (c.1062 + 1G > A). No renal lesions were detected. Case 2 was a 29-year-old man with right pneumothorax, facial papules compatible with fibrofolliculomas, and bilateral renal tumors; genetic testing revealed the frameshift variant FLCN c.1285dupC (exon 11). He underwent bilateral nephron-sparing surgery; pathology showed hybrid oncocytic/chromophobe tumors. These cases illustrate the early-adult spectrum of BHD and support systematic FLCN testing in young patients with recurrent pneumothorax and a BHD-typical cyst pattern, enabling risk-adapted renal surveillance and timely nephron-sparing intervention (Menko et al. in Lancet Oncol 10:1199–1206, 2009; Toro et al. in Arch Dermatol 135:1195–1202, 1999; Zbar et al. in Cancer Epidemiol Biomarkers Prev 11:393–400, 2002; Houweling et al. in Br J Cancer 105:1912–1919, 2011).