Hereditary medullary thyroid carcinoma: how molecular genetics made multiple endocrine neoplasia type 2 a paediatric disease.

Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disorder associated with nearly 100% of lifetime risk of medullary thyroid carcinoma (MTC). MTC is the first tumour of the syndrome to manifest, it shows a nearly 100% penetrance and is the most common cause of death in patients with MEN 2. MEN 2A accounts for over 60-90% of patients with hereditary MTC and is characterized by a combination of MTC, pheochromocytoma and parathyroid adenoma. MEN 2B has a high risk of MTC, pheochromocytoma and includes additional clinical features such as mucosal neuromas, ganglioneuromatosis of the gastrointestinal tract, and a marfanoid habitus. Familial MTC, the third subtype of MEN 2, is characterized by MTC in the objective absence of adrenal and parathyroid gland involvement. The identification of the RET proto-oncogene as the susceptibility gene for MEN 2 has fundamentally changed diagnosis and treatment of the disease since 1993. Availability of genetic screening of at-risk children in MEN 2 kindreds made prophylactic thyroidectomy in asymptomatic mutation carriers possible and genotype-phenotype correlations led to codonoriented prophylactic surgery. In this context, MEN 2 has become a disease of the young child.