Genetic testing for familiar medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia type 2 (MEN 2)
	Identification of RET proto-oncogen mutations as the cause of familiar medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia type 2 (MEN 2) has enabled genetic testing for identification of gene carriers before clinical manifestation of disease. In addition, patients with apparent non-familiar forms of medullary thyroid cancer can be screened for the presence of hereditary disease. Mutations within the RET proto-oncogen on chromosome 10q13 have been identified being responsible for 97% of cases with FMTC and MEN 2. In case of the presence of a RET proto-oncogen mutation, development of medullary thyroid carcinoma almost unvariably occurs during the lifetime of the patient. The availability of the test and its highly predictive value allows the adoption of preventive measures. Current recommendations call for total thyroidectomy to be performed in gene carriers possibly before the age of six years. It should be noted that genetic testing is cost effective as compared to biochemical evaluation by calcitonin testing, particularly as subjects with no mutation being detectable can be excluded from long-term biochemical surveillance programmes. Generally, validation of the result by a second independent sample is required. Patients should best be treated at a specialized center. Table 7 briefly summarizes the experience gained at our institution with this novel test in MEN 2 patients. Table 7: Results of genetic testing in patients with MEN 2 treated at our institute and relation to the clinical phenotype. Genetic testing has been performed in collaboration with Dr. W. Hoeppner, Institute for Hormone and Fertilitiy Research, Hamburg, Germany. MTC = medullary thyroid carcinoma, Pheo = pheochromocytoma, pHPT = primary hyperparathyroidism. Mutation (Affected codon and Change in Nucleotide Sequence)  No. of Affected Families  No. of Affected Family Members MTC Pheo pHPT  MEN 2A 634 TGS -> CGC 4 12 10 9 2  MEN 2A 634 TGC -> TAC 3 16 14 4 1  MEN 2A 611 TGC -> TAC 1 2 2 1 0  MEN 2A 620 TGC -> CGC 1 1 1 1 0  MEN 2A 790 TTG -> TTC 1 6 4 3 0  MEN 2B 918 ATG -> ACG 3 3 3 2 0  Out of 68 patients with an apparent sporadic form of medullary thyroid carcinoma, 3 cases turned out to be familiar disease by genetic testing. Thus, genetic screening is recommended in each patient with medullary thyroid carcinoma.