TY - CHAP M1 - Book, Section TI - Multiple Endocrine Neoplasia Type 2 A1 - Waguespack, Steven G. A1 - Grubbs, Elizabeth G. A1 - Hu, Mimi I. A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. PY - 2014 T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Multiple endocrine neoplasia type 2 (MEN2) is caused by a dominantly inherited or de novo activating (gain of function) mutation in the RET proto-oncogene.MEN2A (95% of MEN2 cases) is characterized by the development of medullary thyroid carcinoma (MTC) in greater than 90% of affected patients, pheochromocytoma (PHEO) in up to 50% of cases, and/or primary hyperparathyroidism (PHPT) in up to 20% of mutation carriers. Depending on the specific RET mutation, cutaneous lichen amyloidosis (CLA) and Hirschsprung disease can also occur.MEN2B (5% of MEN2 cases) is characterized by the universal and early development of MTC, high risk of PHEO (up to 50% of cases) and a highly penetrant, distinctive physical appearance.A strong genotype-phenotype correlation exists in MEN2 such that MTC disease severity, the likelihood of developing PHEO and PHPT, and the age of disease onset can be estimated based on genetic testing results.In RET mutation carriers, C-cell hyperplasia is the initial stage of tumor development that leads to microscopic noninvasive MTC (usually bilateral) and ultimately to lymph node and distant metastases due to frankly invasive carcinoma.Familial MTC (FMTC) is currently considered to be a phenotypic variant of MEN2A with a high risk for MTC but decreased penetrance and/or delayed onset of the other neoplastic manifestations. There is significant overlap between RET mutations associated with FMTC and those of MEN2A. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessmedicine.mhmedical.com/content.aspx?aid=1102701459 ER -