title: From medical history and biochemical tests to presymptomatic treatment in a large MEN 2A family.
abstract: An extensive study was published in 1959 in the Netherlands on a large family, which initially attracted attention because of a family history of attacks of shaking. Clinical investigation revealed phaeochromocytomas in four family members. In 1975, the family was identified to be a MEN 2A family, and since then, the members were examined annually using measurement of catecholamine metabolites in 24-h excreted urine and C-cell stimulation tests. In 1993, the RET proto-oncogene on chromosome 10q11 was found to be associated with MEN 2A and a specific mutation in this gene was identified in the family. In this family, 32 MEN 2A patients were detected. Since screening started in 1975, no patient died of phaeochromocytoma; however, two patients died of metastasized medullary thyroid carcinoma (MTC) (mean age 46 years). Twelve patients were operated on for phaeochromocytoma, and 13 for MTC. The results of DNA-analysis revealed the failures of the biochemical tests to identify affected family members. Six disease gene carriers with normal C-cell stimulation test results appeared to have small multifocal MTCs. Two carriers with normal excretion levels of catecholamines had a small phaeochromocytoma. DNA-analysis enables the unambiguous diagnosis of MEN 2A gene carrier-ship, allowing presymptomatic surgery for MTC.
authors.affiliation: Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lips
authors.forename: R M
authors.initials: RM
authors.lastname: Landsvater
authors.forename: J W
authors.initials: JW
authors.lastname: Höppener
authors.forename: R A
authors.initials: RA
authors.lastname: Geerdink
authors.forename: G H
authors.initials: GH
authors.lastname: Blijham
authors.forename: J M
authors.initials: JM
authors.lastname: Jansen-Schillhorn van Veen
authors.forename: M A
authors.initials: MA
authors.lastname: Feldberg
authors.forename: A P
authors.initials: AP
authors.lastname: van Gils
authors.forename: H
authors.initials: H
authors.lastname: Hoogenboom
authors.forename: M J
authors.initials: MJ
authors.lastname: Berends
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas