Multiple Endocrine Neoplasia Type 2: 2007 Update

<i>Background:</i> Multiple endocrine neoplasia type 2 (MEN-2) is an autosomal dominant tumour syndrome caused by germline-activating mutations of the <i>RET</i> proto-oncogene. It is clinically characterised by the presence of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and primary hyperparathyroidism (MEN-2A) within a single patient. Three distinct clinical forms have been described depending on the phenotype: (1) classic MEN-2A, (2) MEN-2B, an association of MTC, pheochromocytoma and mucosal neuroma and (3) familial MTC (FMTC), which is associated with a low incidence of other endocrinopathies. Each variant of MEN-2 results from a different <i>RET</i> gene mutation, with a good genotype-phenotype correlation. <i>Detection and Treatment:</i> Genetic testing detects nearly 100% of mutation carriers and is considered the standard of care for all first-degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on a three risk-level classification using the genotype-phenotype correlations. <i>Conclusions:</i> MEN-2 provides a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers.