Purpose: The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. Design: We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. Results: Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). Conclusions: The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.
|Autori:||MANNELLI M; CASTELLANO M; SCHIAVI F; FILETTI S; GIACCHÈ M; MORI L; PIGNATARO V; BERNINI G; GIACHÈ V; BACCA A; BIONDI B CORONA G; DI TRAPANI G; GROSSRUBATSCHER E; REIMONDO G; ARNALDI G; GIACCHETTI G; VEGLIO F; LOLI P; COLAO A; AMBROSIO MR; TERZOLO M; LETIZIA C; ERCOLINO T; OPOCHER G|
|Titolo:||Clinically guided genetic screening in a large cohort of italian patients with pheochromocytoma and/or functional or nonfunctional paragangliomas|
|Anno del prodotto:||2009|
|Digital Object Identifier (DOI):||10.1210/jc.2008-2419|
|Appare nelle tipologie:||1.1 Articolo in rivista|