PROLACTINOMAS IN A LARGE KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 - CLINICAL-FEATURES AND INHERITANCE PATTERN

Multiple endocrine neoplasia type 1 (MEN 1) is associated with neoplas ia and hyperfunction of the parathyroid and pituitary glands, pancreat ic islet cells, and neuroendocrine cells of the gut. The inheritance p attern is autosomal dominant, and the underlying genetic defect is sit uated at chromosome 11q13. The MEN 1 gene behaves as a defective copy of a normally constitutive tumor suppressor gene. Development of the M EN 1 phenotype, however, is a multistep and multifactorial process. Th e Tasman 1 genealogy is the largest MEN 1 pedigree detected to date. T hus far, 90 related members with MEN 1 have been screened for evidence of prolactinoma. Prolactinomas were found in 18 patients (20%). Prola ctinomas were not evenly distributed in the genealogy; in 2 branches o f the overall genealogy prolactinomas were present in 50% or more of M EN 1-affected members. The familial distribution of prolactinomas in t hese branches was consistent with an autosomal dominant mode of inheri tance. In the remainder of the pedigree, prolactinomas were uncommon a nd did not display this inheritance pattern. This pedigree represents one of the largest published MEN 1 genealogies in which the risk of de veloping prolactinoma follows an autosomal dominant pattern of transmi ssion. It is the first to demonstrate an inheritance pattern for prola ctinomas acting in addition to, yet distinct from, the inheritance of the underlying MEN 1 gene defect. These findings are consistent with t he existence of an undefined second genetic defect involved in the pat hogenesis of prolactinoma in MEN 1.