title: Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients.
abstract: Head and neck paragangliomas (HNPGLs) are neural crest-derived tumors. In comparison with paragangliomas located in the abdomen and the chest, which are generally catecholamine secreting (sPGLs) and sympathetic in origin, HNPGLs are, in fact, parasympathetic in origin and are generally nonsecreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH) and clinical, laboratory (including metanephrines), and instrumental examinations, patients were divided into three groups: a) patients with a positive FH for HNPGL (index cases only), b) patients with a negative FH and multiple HNPGLs (synchronous or metachronous) or HNPGL associated with an sPGL, and c) patients with negative FH and single HNPGL. The ten patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) proved to be SDHD mutation carriers. Among the 53 patients in group c), ten presented with germ-line mutations (three SDHB, three SDHD, two VHL, and two SDHAF2). An sPGL was found at diagnosis or followed up in five patients (6.3%), all were SDHD mutation carriers. No SDHC, SDHA, MAX, and TMEM127 mutations were found. In SDHD mutation carriers, none of the patients affected by HNPGL associated with sPGL presented missense mutations. In conclusion, a positive FH or the presence of multiple HNPGLs is a strong predictor for germ-line mutations, which are also present in 18.8% of patients carefully classified as sporadic. The most frequently mutated gene so far is SDHD but others, including SDHB, SDHAF2, and VHL, may also be affected.
authors.affiliation: Department of Clinical Pathophysiology, University of Florence, 50139 Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Piccini
authors.forename: Elena
authors.initials: E
authors.lastname: Rapizzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bacca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Trapani
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pulli
authors.forename: Valentino
authors.initials: V
authors.lastname: Giachè
authors.forename: Benedetta
authors.initials: B
authors.lastname: Zampetti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lucci-Cordisco
authors.forename: Letizia
authors.initials: L
authors.lastname: Canu
authors.forename: Elisa
authors.initials: E
authors.lastname: Corsini
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Davide
authors.initials: D
authors.lastname: Carrara
authors.forename: Valeria
authors.initials: V
authors.lastname: Tantardini
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Parenti
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Carlo
authors.initials: C
authors.lastname: Pratesi
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bernini
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016009:Chi-Square Distribution; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010235:Paraganglioma / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D013385:Succinate Dehydrogenase