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.
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.
Authors: Jay S Fonte; Jeremyjones F Robles; Clara C Chen; James Reynolds; Millie Whatley; Alexander Ling; Leilani B Mercado-Asis; Karen T Adams; Victoria Martucci; Tito Fojo; Karel Pacak Journal: Endocr Relat Cancer Date: 2012-02-13 Impact factor: 5.678
Authors: Iñaki Comino-Méndez; Luis J Leandro-García; Guillermo Montoya; Lucía Inglada-Pérez; Aguirre A de Cubas; María Currás-Freixes; Carolyn Tysoe; Louise Izatt; Rocío Letón; Álvaro Gómez-Graña; Veronika Mancikova; María Apellániz-Ruiz; Massimo Mannelli; Francesca Schiavi; Judith Favier; Anne-Paule Gimenez-Roqueplo; Henri J L M Timmers; Giovanna Roncador; Juan F Garcia; Cristina Rodríguez-Antona; Mercedes Robledo; Alberto Cascón Journal: J Mol Med (Berl) Date: 2015-06-14 Impact factor: 4.599
Authors: Jennifer M Kalish; Laura K Conlin; Sogol Mostoufi-Moab; Alisha B Wilkens; Surabhi Mulchandani; Kristin Zelley; Megan Kowalski; Tricia R Bhatti; Pierre Russo; Peter Mattei; William G Mackenzie; Virginia LiVolsi; Kim E Nichols; Jaclyn A Biegel; Nancy B Spinner; Matthew A Deardorff Journal: Am J Med Genet A Date: 2013-03-26 Impact factor: 2.802