Phenotype of the C634Y mutation in the RET proto-oncogene in MEN2A: report of a family

• Published in: Endocrinologia y nutricion Vol. 58; no. 5; p. 229
• Main Authors: Sánchez Sobrino, Paula, Páramo Fernández, Concepción, Gil Gil, Pedro, Mantiñán Gil, Beatriz, Pérez Pedrosa, Alberto, Palmeiro Carballeira, Regina, García-Mayor, Ricardo V
• Format: Journal Article
• Language: Spanish
• Published: Spain 01-05-2011
• Subjects: Adult; Child; Humans; Multiple Endocrine Neoplasia Type 2a - genetics; Mutation; Pedigree; Phenotype; Proto-Oncogene Proteins c-ret - genetics; Retrospective Studies
• ISSN: 1579-2021
• DOI: 10.1016/j.endonu.2011.03.003

Genetic testing of RET proto-oncogen allows an early diagnosis of Multiple Endocrine Neoplasia syndrome type 2 and establish a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of an early diagnosis with genetic testing followed by prompt surgery on the cure of MTC versus a later diagnosis with serum calcitonin.
Retrospective descriptive study of 8 members of a MEN 2A family by C634Y mutation. We performed serum calcitonin screening until 1999 and subsequently RET genetic testing was obtained. Carriers underwent total thyroidectomy and periodic determination of calcitonin, urinary metanephrines, calcium, phosphorus and neck and abdominal imaging techniques.
Five patients were diagnosed by calcitonin familial screening and all of them have high calcitonin by now. Three patients were diagnosed by genetic testing (an adult and two children) and they are free of disease. Calcitonin was closely monitored in children and they underwent surgery when it started to raise, at 6 and 10 years old respectively, finding nodular C-cell hyperplasia in both. Of 8 carriers 3 developed pheochromocytomas, bilateral and asynchronous, one-half had normal urinary metanephrines and two of them were simultaneous with MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy.
RET genetic analysis has achieved an early diagnosis and treatment with no development of MTC in our patients, adjusting the time and type of surgery and allowing a genotype-phenotype correlation. It demonstrates how a genetic alteration is associated with a pathology that we can prevent and manage improving the prognosis of our patients.