January - March 2007, Volume 3, Issue 1

Radian S, Badiu C, Capatina C, Coculescu M, Grigorescu F

Molecular diagnosis of multiple endocrine neoplasia (MEN) type 2A: implementation of mutation detection in RET oncogene and challenges in the management of affected individuals

Acta Endo (Buc) 2007, 3 (1): 13-22
doi: 10.4183/aeb.2007.13

Introduction. Multiple Endocrine Neoplasia type 2A (MEN 2A) is a rare genetic autosomal dominant disease caused by mutations of RET gene (Chr 10q11.21). Clinical features include medullary thyroid carcinoma (MTC) with 90-95% penetrance, pheochromocytoma (50% penetrance) and primary hyperparathyroidism (20-30%). Screening for RET gene mutation allows early identification of asymptomatic carriers who may benefit from prophylactic thyroidectomy, thus preventing morbidity and death.\r\nAim. Implementation of RET mutation detection as screening procedure for Romanian MEN 2A families.\r\nSubjects and methods. We studied a three-generation MEN 2A Romanian family with one affected male (age 75) in the first generation, his affected descendants (one male-45y, one female-42y old) in the second generation and four asymptomatic subjects at risk (three males aged 15, 19 and 22y and one 18y old female) in the third generation. Mutation detection was performed by automated DNA sequencing of PCR-amplified exons 10 and 11 of RET gene.\r\nResults. A Cys634Arg (TGC/CGC) heterozygous mutation of RET gene was detected in affected individuals as well as in 3 asymptomatic male subjects, but was absent in one asymptomatic female. Sequencing results were confirmed by digestion of PCR products with HhaI restriction enzyme. Total thyroidectomy was proposed to all asymptomatic carriers, although this decision was postponed and patients continued biochemical screening.\r\nConclusion. Despite success in implementation of mutation detection in clinical laboratory, this study illustrates the difficulty in acceptance of prophylactic thyroidectomy by mutation carriers. Written information, genetic counseling in a familial setting and patient support groups could all contribute to improve acceptance of prophylactic treatment.

Keywords: MEN2A, RET, prophylactic, thyroidectomy, counseling, screening

Correspondence: Serban Radian, M.D., 34-35 Bd. Aviatorilor, 011863, Bucharest, Sector 1, Romania, e-mail: serban.radian@montp.inserm.fr