CLINICAL AND MOLECULAR-FEATURES OF THE HEREDITARY MIXED POLYPOSIS SYNDROME

Background & Aims: Various inherited syndromes predispose to the devel opment of colonic juvenile polyps and colorectal cancer, with potentia l importance for sporadic tumorigenesis, This study describes features of a possibly new syndrome of atypical juvenile polyps and other colo nic tumors and compares these features with those of known gastrointes tinal tumor syndromes, Methods: A large family, St, Mark's family 96, with a tendency to develop colonic polyps of mixed histological types is described, Genetic linkage to known polyposis syndromes has been te sted, Results: Adenomatous and hyperplastic polyps occur in affected m embers of the family, although the characteristic lesion is an atypica l juvenile polyp. Some affected individuals have developed polyps of m ore than one type, and individual polyps may contain features of more than one histological type, Polyps can undergo malignant change. Typic ally, fewer than 15 polyps are found at colonoscopy and there is no ex tracolonic disease associated with the development of polyps, The fami ly's polyps seem to be inherited in an autosomal-dominant fashion, but the disease is probably unlinked to candidate loci with importance in colorectal tumorigenesis, such as APC, hMSH2, and hMLH1. Conclusions: We term this family's disease hereditary mixed polyposis syndrome (HM PS). Although mutations in the putative HMPS gene may be responsible f or syndromes such as juvenile and Peutz-Jeghers polyposes, HMPS may al so be a distinct disease.