title: Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department Clinical Pathophysiology, University of Florence, Viale Pieraccini 5, 50139 Florence, Italy. m.mannelli@dfc.unifi.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Castellano
authors.forename: Francesca
authors.initials: F
authors.lastname: Schiavi
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Mara
authors.initials: M
authors.lastname: Giacchè
authors.forename: Luigi
authors.initials: L
authors.lastname: Mori
authors.forename: Viviana
authors.initials: V
authors.lastname: Pignataro
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Bernini
authors.forename: Valentino
authors.initials: V
authors.lastname: Giachè
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bacca
authors.forename: Bernadette
authors.initials: B
authors.lastname: Biondi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Trapani
authors.forename: Erika
authors.initials: E
authors.lastname: Grossrubatscher
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Reimondo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arnaldi
authors.forename: Gilberta
authors.initials: G
authors.lastname: Giacchetti
authors.forename: Franco
authors.initials: F
authors.lastname: Veglio
authors.forename: Paola
authors.initials: P
authors.lastname: Loli
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Letizia
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Opocher
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D005787:Gene Frequency; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000453:epidemiology / Q000235:genetics*; D010673:Pheochromocytoma / Q000453:epidemiology / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D004247:DNA