Objectives Genetic screening for germ-line mutations in the RET proto-oncogene has been extensively exploited worldwide to optimize the diagnostic and clinical management of multiple endocrine neoplasia type 2(MEN 2)patients and their relatives.However,a distinct lag period exists not only in the recognition but also in the medical treatment of patients with MEN 2.Here we present a comprehensive genetic and clinical analysis of MEN 2 among Chinese families followed from 1975 to 2011.Methods Our series comprises thirty-six index cases and 134 relatives from 11 independent families.Genetic diagnosis was performed in all participants by direct sequencing all relevant RET exons.Thyroidectomy was performed in 50 patients with varying cervical neck dissection procedures.Patients with pheochromocytoma underwent specific surgery.Demographic,clinical profiles,mutation types,tumor histopathologic features and follow-up records were systematic analyzed.Results The PET mutations p.C634Y(n=34),p.C634R(n=6),p.C618S(n=13),p.V292M/R67H/R982C(n=7),p.L790F(n=2)and p.C634Y/V292M/R67H/R982C(n=1)were confirmed in 31 index cases and then identified in 32 at-risk relatives(mutation carriers),with MEN 2A as the most common clinical subtype.The overall penetrance ofpheochromocytoma in patients with MEN 2A was 46.7%.A total of 50 patients underwent thyroidectomy and there was a significant lowering of their mean age at thyroidectomy and tumor diameter of the mutation carriers that were detected and operated on compared with the index cases [age at first surgery:29.3 vs 39.3 years,P<0.05;maximum size:1.1 vs 3.3 cm,P<0.001].There was also a decrease in the TNM staging and the proportion of patients who underwent inappropriate initial thyroid surgery [pN1:31.6% vs 100%,P<0.001;inappropriate surgery:0% vs 29%].Meanwhile,disease-free survival(DFS)increased [DFS:100% vs 58.1%,P<0.05].Both MTC-specific(n=1)and pheochromocytoma-specific(n=5)mortality were reported during the study period.Conclusion Our results further substantiate that gene scanning of all relevant RET exons is a powerful tool in the management of MEN 2 patients,especially in asymptomatic carriers,and has led to earlier diagnosis and more complete initial treatment of patients with MEN 2 in China.