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Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and hyperplasia and/or neoplasia of other endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been estimated at approximately 1/30 000. Two different forms, sporadic and familial, have been described for MEN2. The sporadic form is represented by a case with two of the principal MEN2-related endocrine tumors. The familial form, which is more frequent and displays an autosomal dominant pattern of inheritance, consists of a MEN2 case with at least one first-degree relative with one of the characteristic endocrine tumors. Familial medullary thyroid carcinoma (FMTC) is a subtype of MEN2 in which the affected individuals develop only medullary thyroid carcinoma, without other clinical manifestations of MEN2. Predisposition to MEN2 is caused by germline activating mutations of the c-RET proto-oncogene on chromosome 10q11.2. The RET gene encodes a single-pass transmembrane tyrosine kinase that funtions as the receptor for glial-derived neurotrophic growth factors. The combination of clinical and genetic investigations, together with the improved understanding of the molecular and clinical genetics of the syndrome, has assisted the diagnosis and treatment of patients. DNA testing makes early detection of asymptomatic gene carriers possible and allows identification and treatment of the neoplastic lesions at an earlier stage. In particular, the identification of a strong genotype-phenotype correlation in MEN2 syndrome may enable a more individualized treatment to be developed for the patients, improving their quality of life. At present, surgical treatment offers the only chance of a cure and therefore, early clinical and genetic detection and prophylactic surgery in subjects at risk are the main therapeutic goals. |