Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by loss-of-function of the MEN1 gene, a tumor suppressor gene encoding for the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas (ADR) and bronchopulmonary (bp-NET), thymic and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs.To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands.All Dutch MEN1 families with ≥ ten affected members in ≥ two successive generations were identified. Age at detection of the different MEN1 related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared.A total of 152 MEN1 patients from ten families were included. A significantly decreased age at detection of pHPT, dpNET, PIT and bp-NET was found in successive generations (P < 0.0001). Adjusted analyses led to the same results.These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future more personalized screening protocols and earlier screening for future generations of MEN1 patients.