The clinical diagnosis of MEN2A is made when an individual has two or more specific endocrine tumors: medullary carcinoma of the thyroid (>95%), pheochromocytoma (50%), or parathyroid adenoma/hyperplasia (20-30%). Prophylactic thyroidectomy in childhood is recommended when a RET mutation is identified.
FMTC (Familial Medullary Thyroid Carcinoma) is diagnosed in families with four cases of medullary thyroid carcinoma (MTC) in the absence of pheochromocytoma or parathyroid adenoma. The medullary thyroid cancer associated with FMTC is typically later onset and may be subclinical; therefore, in some families RET genetic testing may be necessary to differentiate sporadic medullary thyroid cancer from FMTC.
RET gene mutations also are associated with two other distinct disorders, MEN2B and Hirschsprung disease (see separate information sheets for GeneDx testing information), and in approximately 10% of isolated pheochromocytoma. Predisposition to pheochromocytoma is shared by other cancer predisposition syndromes, including Von Hippel Lindau syndrome (VHL gene), Hereditary PGL/PCC syndrome (SDHD, SDHB, SDHC genes), NF1 (NF1 gene) and rarely Carney Complex (PRKAR1A gene). Testing for all of these syndromes, with the exception of NF1, is available at GeneDx.