Pathogenic variants in the MEN1 gene (ClinGen DEFINITIVE) cause MEN1. GeneReviews documents menin as a tumor suppressor with a two-hit loss-of-heterozygosity mechanism. No reliable genotype-phenotype correlations per GeneReviews. ClinVar: 125 pathogenic and 30 likely pathogenic variants.

Per GeneReviews, diagnostic criteria include: two or more MEN1-associated endocrine tumors; or one such tumor with an affected first-degree relative; or a germline pathogenic MEN1 variant. Biochemical surveillance begins in childhood for at-risk individuals per GeneReviews.

No FDA-approved targeted therapies are documented in this packet for MEN1. Per GeneReviews, management involves subspecialty surveillance and treatment of individual tumor types. Documented management modalities include parathyroid surgery, proton pump inhibitors for gastrinoma management, somatostatin analogs for entero-pancreatic tumors, dopamine agonists for prolactinomas, and systemic therapies for advanced disease per GeneReviews.

Per GeneReviews, mortality is most commonly due to malignant entero-pancreatic tumors or thymic carcinoids. Penetrance is age-dependent: approximately 50% of gene carriers have manifestations by age 20 and 95% by age 40.

Three trials documented: NCT04124107 (observational, pituitary tumors in pediatric MEN1, Groupe d'etude des Tumeurs Endocrines); NCT07174757 (Phase 2 lanreotide study, NIH Clinical Center, enrollment August 2025, completion July 2030); NCT07325456 (observational young adult surveillance study, University of Michigan, March 2026 to March 2031).