Clinical and Genetic Experience in Turkish Multiple Endocrine Neoplasia Type 2 Families

Abstract

Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the ret proto-oncogene. Identification of the germline mutation is crucial for the diagnosis and management of MEN 2. Fifteen independent families with MEN 2 (12 families with MEN 2A, 1 family with FMTC, and 2 families with MEN 2B) were studied for the spectrum of the ret proto-oncogene mutations, clinical presentation, and management strategy. Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. Two MEN 2B families showed classic Met918Thr mutation in exon 16. One familial MTC family revealed Val804Leu mutation in exon 14. Genetic testing was offered for at-risk family members. Overall 41 subjects were found to be positive for the ret proto-oncogene mutations. From these families, 30 patients underwent MTC surgery at a median age of 33 years (range, 2 months to 58 years); lymph node metastases were found in 7 patients. The presence of MTC in the thyroid gland removed prophylactically from a 2-month-old girl with MEN 2B and a 4.5-year-old girl with MEN 2A highlights the importance of intervention. Nineteen patients presented with pheochromocytoma. Only 1 MEN 2A family showed primary hyperparathyroidism. Genetic screening should be a routine part of the diagnosis and management of MEN 2 syndromes. The observed ret mutations and the clinical characteristics of these diseases in Turkish families were similar to those previously reported from other populations. Prophylactic thyroidectomy based on genetic testing should be performed in the first year of life in MEN 2B and before 4 years of age in MEN 2A.