Caracterização molecular de uma família com nem2a e suas implicações clínicas.

Resumo

MEN2A is an autossomal dominant cancer syndrome characterised by the presence of medullary thyroid cancer, pheochromocytoma and primary hyperparathyroidism. Germline mutations of the RET protooncogene constitute the molecular defect and can be identified in affected individuals. Genetic screening of family members at risk allows early diagnosis and preventive measures before the appearance of the disease. We present a family with several members affected with MEN2A, their molecular characterisation and the clinical implications of genetic testing.We studied 18 members distributed among three generations of a family of which four members were clinically affected with MEN2A and cutaneous lichen amyloidosis. RET gene mutations were screened for in affected individuals and their offspring by PCR-RFLP techniques.Genetic testing revealed a point mutation at codon 634 (TGC>TGG), in the heterozygous state, in all affected individuals. The same mutation was also found in a five years old asymptomatic child which after total thyroidectomy showed to have multifocal medullary thyroid carcinoma.Genetic screening is the most suitable method for pre-symptomatic diagnosis of MEN2A allowing an efficient and early identification of individuals who will later develop the disease. These can be monitored more closely and be submitted to a prophylactic thyroidectomy before the appearance of medullary thyroid carcinoma. The ideal moment for this intervention is still under discussion although the results of this study suggest that it should be undertaken before the age of five.