ATA Guidelines Tools

1 Diagnosis Î The current ATA risk categories for hereditary MTC should be changed. • The current level D category should be changed to a new category, "highest risk" (HST), that includes patients with MEN2B and the RET codon M918T mutation. • The current level C category should be changed to a new category, "high risk" (H), that includes patients with MEN 2A and RET codon C634 mutations. • The current level A and B categories should be combined into a new category "moderate risk" (MOD) that includes patients with hereditary MTC and RET codon mutations other than M918T and C634. (C) Î There should be two MEN2 syndromes: MEN2A and MEN2B. Within MEN2A, which accounts for 95% of MEN2 cases, there should be four variants: 1. Classical MEN2A (represented by the uniform presence of MTC and the less frequent occurrence of pheochromocytoma (PHEO), or hyperparathyroidism HPTH, or both) 2. MEN2A with cutaneous lichen amyloidosis (CLA). 3. MEN2A with Hirschsprung's Disease (HD). 4. FMTC (families or individuals with RET germline mutations who have MTC but neither PHEOs or HPTH). (C) Î The recommended method of initial genetic testing for MEN2A is either a single or multi-tiered analysis to detect RET mutations in exon 10 (codons 609, 611, 618, and 620), exon 11 (codons 630 and 634), and exons 8, 13, 14, 15, and 16. (B) The most common RET mutations associated with MEN2A and MEN2B are shown in Table 2. Î Sequencing of the entire coding region should be reserved for situations where no RET mutation is identified, or there is a discrepancy between the MEN2 phenotype and the expected genotype. (B) Î Patients with the MEN2B phenotype should be tested for the RET codon M918T mutation (exon 16), and if negative, the RET codon A883F mutation (exon 15). If there are no mutations identified in these two exons the entire RET coding region should be sequenced. (B) Î Patients with presumed sporadic MTC should have genetic counseling and genetic testing to detect a RET germline mutation. (B) Î Genetic counseling and genetic testing for RET germline mutations should be offered to: a) first degree relatives of patients with proven hereditary MTC b) parents whose infants or young children have the classic phenotype of MEN2B c) patients with CLA d) infants or young children with HD and exon 10 RET germline mutations e) adults with MEN2A and exon 10 mutations who have symptoms suggestive of HD. (B)

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