SAJS OCTOBER 2010.indd

127 Multiple endocrine neoplasia type 2 (MEN2) syndromes are autosomally dominant clinical associations characterised by a number of tumours, including medullary thyroid carcinoma (MTC), phaeochromocytoma, thyroid C-cell hyperplasia (CCH), parathyroid tumours (MEN2A) and ganglioneuroma of the gastrointestinal tract (MEN2B). The common factor in the MEN2 syndromes is MTC, a poorly differentiated thyroid malignancy that represents 3 10% of thyroid tumours but is hereditary in 20 30% of cases. MTC (and other thyroid tumours) have been shown to be genetically linked to mutations in the RET (REarranged during Transfection) proto-oncogene (situated at 10q22), which plays a pivotal role in at least four clinical syndromes (MEN2A and MEN2B, familial medullary thyroid carcinoma (FMTC) and Hirschsprung’s disease (HSCR)) in a unique ‘switch on, switch off ’ manner. RET gene variations are present in more than 50% of MTC cases as well as a significant number of papillary thyroid carcinomas (chromosomal inversions or translocations (RET/ PTC). Inheritance is important, and the risk to family members appears to be particularly high in MEN2. Patients with genetic mutations involving the cysteine radicals of the gene account for 92 95% of those who later develop MTC. Children of families with MTC and the MEN2 syndromes have been reported to Chasing the ubiquitous RET proto-oncogene in South African MEN2 families – implications for the surgeon