title: Familial medullary thyroid carcinoma: presymptomatic diagnosis and management in children.
abstract: Two kindreds with familial medullary thyroid carcinoma (MTC) are described in which affected family members had variable clinical and pathologic manifestations. Genetic testing in 2 children from one kindred revealed a mutation in exon 10, codon 618 (TGC to AGC) in the extracellular cysteine-rich region of the RET gene. In this kindred an 11-year-old had microscopic evidence of MTC; however, a 17-year-old had no evidence of pathology on thyroidectomy. 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 disease and C-cell hyperplasia to carcinoma with lymph node metastasis; a 7-year-old with the mutation and a normal response to provocative testing was also identified. Management recommendations in children from families with clearly defined familial MTC may be individualized to reflect emerging genotype-phenotype correlations.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8000, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Heptulla
authors.forename: R P
authors.initials: RP
authors.lastname: Schwartz
authors.forename: A E
authors.initials: AE
authors.lastname: Bale
authors.forename: S
authors.initials: S
authors.lastname: Flynn
authors.forename: M
authors.initials: M
authors.lastname: Genel
mesh_terms: D000293:Adolescent; D000328:Adult; D018276:Carcinoma, Medullary / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy