Familial medullary thyroid carcinoma: Presymptomatic diagnosis and management in children

Two kindreds with familial medullary thyroid carcinoma (MTC) are described in which affected family members had variable clinical and pathologic manif estations. Genetic testing in 2 children from one kindred revealed a mutati on in exon 10, codon 618 (TGC to AGC) in the extracellular cysteine-rich re gion of the RET gene. In this kindred an 11-year-old had microscopic eviden ce of MTC; however, a 17-year-old had no evidence of pathology on thyroidec tomy. In a second kindred a rare mutation in exon 14, codon 804 (GTG to TTG ) of the intracellular tyrosine kinase region of the RET gene was detected. In this kindred MTC has occurred in the 4th to 5th decades of life, with a clinical spectrum in mutation-positive family members ranging from no dise ase and C-cell hyperplasia to carcinoma with lymph node metastasis; a 7-yea r-old with the mutation and a normal response to provocative testing was al so identified. Management recommendations in children from families with cl early defined familial MTC may be individualized to reflect emerging genoty pe-phenotype correlations.