Hereditary leiomyomatosis and renal cell cancer (HLRCC), pheochromocytoma (PCC)/paraganglioma (PGL) and germline fumarate hydratase (FH) variants

HLRCC, an autosomal dominant condition caused by germline P/LP variants in the fumarate hydratase (FH) gene, is characterized by multiple cutaneous and uterine leiomyomas and RCC.0.6-3.1% of individuals with PCC/PGL carry a germline P/LP variant in the FH gene.Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do.Preliminary evidence suggests that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and that patients with HLRCC should be screened for PCC/PGL.Until more information becomes available, we suggest doing a full history, physical, family history, and screen for HLRCC-associated manifestations when there is an FH variant.Screening for PCC/PGL in patients with HLRCC could potentially include a baseline whole-body MRI and plasma fractionated metanephrines.