Multiple endocrine neoplasia type 2 (MEN2) in children and adolescents

Background: Multiple endocrine neoplasia (MEN) type 2 is a rare autosomal d ominant inherited tumor disorder, which is subclassified into MEN type 2a, MEN type 2b and FMTC (familial medullary thyroid carcinoma). Tumor developm ent in MEN type 2 is caused by activating mutations of the RET-protooncogen e, located on chromosome 10. Apart from medullary thyroid carcinoma (MTC),w hich is the only disease manifestation in FMTC,affected individuals may als o suffer from phaeochromocytoma in MEN type 2a and 2b and primary hyperpara thyroidism in type 2a. Characteristical features for MEN type 2b,which is o ften caused by de-novo mutations,are mucosal neurinomas and a marfanoid phy sical appearance. Patients: The 9 patients with MEN type 2a and FMTC described here (age 4-15 y.) were identified as gene-carriers by family screening and had no clinic al symptoms yet. In 6 patients mutations in exon 11 (codon 634, cystine>arg inine or cystine>tyrosine) of the RET-proto-oncogene were found, 3 patients showed mutations in exon 14(codon 804, valine>methionine). In 5 children w ith elevated plasma calcitonin concentrations thyroidectomy revealed C-cell -hyperplasia (CCH) in all cases,one girl had MTC and in addition a unilater al phaechromocytoma .3 out of 4 children with normal calcitonin values unde rwent thyroidectomy so far, one had CCH. In the remaining 2 no pathologic h istological changes were found. All 3 patients with MEN type 2b (age 4-16 y .) showed a typical phenotype and had metastasizing MIC. None of these surv ived, the youngest died at the age of 5 years. Discussion: Today gene-carder status for MEN type 2 can be detected reliabl y by mutation analysis of the RET-proto-oncogene. Prophylactic thyroidectom y in affected individuals may prevent the development of MTC. Because of th e high malignancy of MTC in MEN type 2b early diagnosis and immediate thyro idectomy are crucial. All patients with MEN type 2 must be kept under endoc rinological control because of the risk of relapse after surgery and/or the development of associated tumors.