Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are major genetic 
disorders carrying a high risk of endocrine tumor development. The mutated genes 
were identified in 1993 (MEN2-RET) and 1997 (MEN1), enabling genetic testing and 
functional studies. Genetic analysis has led to new clinical and therapeutic 
strategies for MEN1/2 patients, and has improved our understanding of the 
pathways underlying the development of such tumors, which occur in an autosomal 
dominant manner and with high penetrance. The MEN1 gene encodes menin, a protein 
involved in many cell functions, such as transcription, genome stability, cell 
cycling and apoptosis. The MEN1 gene has 10 exons, and its exhaustive analysis 
in MEN1 patients helps guide their management. MEN2 is related to activating 
missense mutations in the RET protooncogene, which encodes a tyrosine kinase 
receptor (TKR). RET activation occurs upon autodimerization induced by the 
binding of specific ligands belonging to glial cell-derived neurotrophic 
factor-like family (GFL) proteins, regulated by coreceptors. The position of 
missense mutations--in the extracellular or intracellular TK domains--influences 
the aggressiveness of the most frequent malignancy, medullary thyroid carcinoma, 
establishing a genotype-phenotype correlation. We also briefly describe the 
genetic basis of three other inherited states predisposing individuals to 
endocrine tumors, namely Carney's syndrome, hyperparathyroidism type 2 (HRPT2) 
and familial isolated pituitary adenoma (FIPA), which are related to 
inactivating mutations in the PRKAR1-alpha, HRPT2 and AIP genes, respectively.