BACKGROUND: Genetic screening for germline mutations in the RET proto-oncogene 
has been extensively exploited worldwide to optimize the diagnostic and clinical 
management of multiple endocrine neoplasia type 2 (MEN2) patients and their 
relatives. However, a distinct lag period exists not only in the recognition but 
also in the medical treatment of patients with MEN2. Here we present a 
comprehensive genetic and clinical analysis of MEN2 among Chinese families 
followed from 1975 to 2011. Our series comprises 36 index cases and 134 
relatives from 11 independent families.
METHODS: 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 
(PHEO) underwent specific surgery. Demographic, clinical profiles, mutation 
types, tumor histopathologic features, and follow-up records were systematically 
analyzed.
RESULTS: The RET 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 MEN2A as the most common clinical subtype. The overall 
penetrance of PHEO in patients with MEN2A was 46.7%. A total of 50 patients 
underwent thyroidectomy, and there was a significant lowering of their mean age 
at thyroidectomy and the 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 medullary thyroid 
carcinoma-specific (n=1) and PHEO-specific (n=5) deaths were reported during the 
study period.
CONCLUSIONS: Our results further substantiate that gene scanning of all relevant 
RET exons is a powerful tool in the management of MEN2 patients, especially in 
asymptomatic carriers, and has led to earlier diagnosis and more complete 
initial treatment of patients with MEN2 in China.