Birt-Hogg-Dubé syndrome and Smith-Magenis syndrome both involve the 17p11.2 chromosomal region, with FLCN germline pathogenic variants causing Birt-Hogg-Dubé syndrome and RAI1 deletions causing Smith-Magenis syndrome. When Smith-Magenis syndrome deletions extend to include FLCN, Birt-Hogg-Dubé syndrome-related manifestations may develop; however, such occurrences remain anecdotal, particularly with respect to renal tumors. We describe a 35-year-old man with Smith-Magenis syndrome who developed two right renal tumors, including one confirmed FLCN-mutated tumor. Histology revealed a mosaic admixture of oncocytic and chromophobe-like cells with patchy keratin 7 and KIT expression. Molecular analysis identified a germline 17p11.2 deletion encompassing FLCN and RAI1, together with a somatic FLCN splice-donor mutation (c.1300+1G>A), consistent with biallelic FLCN inactivation. These findings support a shared pathogenic mechanism between Smith-Magenis syndrome and Birt-Hogg-Dubé syndrome, contributing to the existing literature on FLCN-associated renal neoplasia. Recognition of this overlap is important for clinical awareness and further supports renal surveillance in Smith-Magenis syndrome patients.
Pichette et al. (2026) studied this question.