Multiple Endocrine Neoplasia Type 2 Definition and Characteristics

Clinical Subtypes and Prevalence

The American College of Medical Genetics and Genomics recommends considering Multiple Endocrine Neoplasia Type 2 (MEN2) as a hereditary cancer syndrome caused by germline mutations in the RET proto-oncogene, with a prevalence of 1:35,000 to 1:40,000 in the general population 1, 6
MEN2 encompasses two main clinical variants: MEN2A (91% of cases), characterized by medullary thyroid carcinoma (MTC) with >95% lifetime risk, pheochromocytoma in 50% of patients, and primary hyperparathyroidism in 20-30% of cases, and MEN2B (9% of cases), the most aggressive form with 100% risk of MTC, 50% risk of pheochromocytoma, and other distinct features 1, 5
The National Comprehensive Cancer Network notes that Familial Medullary Thyroid Carcinoma (FMTC) is now considered a variant of MEN2A with decreased penetrance of pheochromocytoma and hyperparathyroidism, accounting for 35% of MEN2A cases 1, 6

The Endocrine Society states that the syndrome results from activating mutations in the RET proto-oncogene, a receptor tyrosine kinase, with an autosomal dominant inheritance pattern and strong genotype-phenotype correlations 1, 5
The de novo mutation rate is approximately 9% in MEN2A and as high as 50% in MEN2B, according to the American College of Medical Genetics and Genomics 7, 8