All three subtypes impart a high risk for developing MTC. MEN 2A has an increased risk of pheochromocytoma and parathyroid adenoma and/or hyperplasia. MEN 2B has an increased risk of pheochromocytoma and includes additional clinical features such as mucosal neuromas of the lips and tongue, distinctive faces with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and an asthenic Marfanoid body habitus. FMTC has been defined as the presence of at least four individuals with MTC without any other signs or symptoms of pheochromocytoma or hyperparathyroidism in the proband or other family members.
Some families previously classified as FMTC will go on to develop one or more of the MEN 2A-related tumors, suggesting that FMTC is simply a milder variant of MEN 2A. Offspring of affected individuals have a 50% chance of inheriting the genemutation.
The age of onset of MTC varies in different subtypes of MEN 2. MTC typically occurs in early childhood for MEN 2B, predominantly early adulthood for MEN 2A, and middle age for FMTC.
Germline deoxyribonucleic acid (DNA)-based testing of the RET gene (chromosomal region 10q11.2) identifies disease-causing mutations in more than 95% of individuals with MEN 2A and MEN 2B and in about 88% of individuals with FMTC.
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