ABSTRACT
Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant inherited cancer syndrome whose incidence is 1: 500 000 live births. MEN 2 is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. In a known MEN 2 family with an identified family-specific mutation, therefore, the detection of the same mutation in a clinically at-risk individual indicates that that person has MEN 2. Hirschsprung disease (HSCR), characterized by aganglionosis of the gut, was seemingly unrelated to MEN 2. This syndrome is usually sporadic but a proportion are familial as well, although the genetics were felt to be complex. In a syndrome where over 92% of cases have identified germline mutations, it can be uncomfortable when a clinician is faced with a RET mutation-negative MEN 2 family. In general, the germline mutations that characterize MEN 2A and many family medullary thyroid carcinoma are missense mutations which change a cysteine codon to another non-sulfhydryl-containing amino acid.
