Direct molecular diagnosis of multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by the predisposition to develop both peptic ulcer disease and a wide variety of endocrine tumors usually in adolescence and adulthood. Specifically, hyperplasia and/or tumors (most often adenomas) of the parathyroid, pancreatic islet cells, anterior pituitary, and adrenal cortical glands are classically described in affected individuals who have MEN1 (1,2). MEN1 is a highly penetrant disorder whose onset is generally during adult life with the occurrence of at least one, but most often more than one, of the aforementioned tumors. The age-related penetrance of this disorder based on analysis in 63 unrelated kindreds is 7, 52, 87, 98, 99, and 100% by 10, 20, 30, 40, 50, and 60 yr, respectively (3). The disorder is estimated to occur in approx 1 in 30,000 to 1 in 50,000 individuals. Most cases are associated with a positive family history of the disorder, but new germline mutations have been identified in a small percentage of individuals having a negative family history of the disorder but classic features of MEN1 (3-7).