Criteria for mutation analysis in MEN 1-suspected patients: MEN 1 case-finding

Background Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal, dom inantly inherited cancer syndrome, with tumours in various endocrine glands . In 1997 the responsible tumour suppressor gene was identified. MEN1 gene germ-line mutations are detected in the vast majority of MEN 1 patients, ho wever, with regard to case-finding, unfortunately only at a very low freque ncy in patients with apparently sporadic MEN 1-related tumours. In order to increase the detection rate of disease gene carriers among patients with a pparently sporadic MEN 1-related tumours, clinical criteria were needed. Design and Results In this study MEN1 gene germ-line mutations were reveale d in 16/16 MEN 1 patients/families (100%). Based on our clinical experience with MEN 1 patients/families we formulated clinical criteria to identify d isease gene carriers among patients with apparently sporadic MEN 1-related tumours. The criteria for MEN 1-suspected patients are: young age at onset (< 35 years) and/or multiple MEN 1-related lesions in a single organ or two distinct organs affected. Application of these criteria yielded MEN1 gene germ-line mutations in nine of 15 MEN 1-suspected patients (60%), thus iden tifying novel MEN 1 families. Follow up was also guaranteed for patients no t fulfilling these criteria. Conclusions The clinical criteria for MEN 1-suspected patients increase the detection rate of germ-line MEN1 gene mutations among patients with appare ntly sporadic MEN 1-related tumours. These criteria may be used for (presym ptomatic) identification of MEN 1 disease gene-carriers, thus enabling earl y detection of tumour development and timely treatment, as well as genetic counselling.