MEN2 Definition
MEN2 stands for Multiple Endocrine Neoplasia Type 2, a hereditary cancer syndrome caused by germline mutations in the RET proto-oncogene on chromosome 10q11.21 1.
Clinical Subtypes
MEN2 encompasses two main clinical variants with distinct features 1:
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 1
MEN2B (9% of cases): The most aggressive form with 100% risk of MTC (often presenting in infancy), 50% risk of pheochromocytoma, mucosal neuromas, intestinal ganglioneuromatosis, marfanoid habitus, and notably no hyperparathyroidism 1
Familial Medullary Thyroid Carcinoma (FMTC): Now considered a variant of MEN2A with decreased penetrance of pheochromocytoma and hyperparathyroidism, accounting for 35% of MEN2A cases 1
Genetic Basis
The syndrome results from activating mutations in the RET proto-oncogene, a receptor tyrosine kinase 1, 2. The inheritance pattern is autosomal dominant with strong genotype-phenotype correlations 1. The de novo mutation rate is approximately 9% in MEN2A and as high as 50% in MEN2B 2, 3.
Prevalence
The estimated prevalence of MEN2 is 1:35,000 to 1:40,000 in the general population 1.