<i>FLCN</i> -Mutated Tumors in Smith-Magenis Syndrome: A Case Report of <i>FLCN</i> -Associated Pathogenesis

Birt-Hogg-Dubé syndrome and Smith-Magenis syndrome both involve the 17p11.2 chromosomal region, with <i>FLCN</i> germline pathogenic variants causing Birt-Hogg-Dubé syndrome and <i>RAI1</i> deletions causing Smith-Magenis syndrome. When Smith-Magenis syndrome deletions extend to include <i>FLCN</i>, 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 <i>FLCN</i>-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 <i>FLCN</i> and <i>RAI1</i>, together with a somatic <i>FLCN</i> splice-donor mutation (c.1300+1G>A), consistent with biallelic <i>FLCN</i> inactivation. These findings support a shared pathogenic mechanism between Smith-Magenis syndrome and Birt-Hogg-Dubé syndrome, contributing to the existing literature on <i>FLCN</i>-associated renal neoplasia. Recognition of this overlap is important for clinical awareness and further supports renal surveillance in Smith-Magenis syndrome patients.