Multiple Endocrine Neoplasia Syndromes

Multiple endocrine neoplasia (MEN) syndromes are inherited disorders that predispose a person to tumors in more than one endocrine organ. The clinical danger is not simply “multiple tumors.” Each tumor may secrete hormones, compress nearby structures, or become malignant, and the family implications extend across generations. MEN1 and MEN2 have very different molecular causes and clinical patterns. - MEN1 results from germline loss-of-function variants in the MEN1 tumor-suppressor gene. Loss of tumor-suppressor function removes a brake on cellular growth. - MEN2 results from germline activating variants in the RET proto-oncogene. An activated RET pathway behaves more like a growth signal that is permanently switched on. Both syndromes warrant genetic counseling, testing of the affected person, and cascade testing of first-degree relatives. A pathogenic variant can identify an at-risk relative before symptoms or tumors develop, allowing surveillance and preventive treatment at the age when it can change outcomes. For children in MEN1 families, genetic testing is generally considered during the first decade of life. This timing allows meaningful surveillance while recognizing the psychological burden of testing a child for an adult-onset...