title: High prevalence of occult paragangliomas in asymptomatic carriers of SDHD and SDHB gene mutations.
abstract: Hereditary paraganglioma is a benign tumor syndrome with an age-dependent penetrance. Carriers of germline mutations in the SDHB or SDHD genes may develop parasympathetic paragangliomas in the head and neck region or sympathetic catecholamine-secreting abdominal and thoracic paragangliomas (pheochromocytomas). In this study, we aimed to establish paraganglioma risk in 101 asymptomatic germline mutation carriers and evaluate the results of our surveillance regimen. Asymptomatic carriers of an SDHD or SDHB mutation were included once disease status was established by MRI diagnosis. Clinical surveillance revealed a head and neck paraganglioma in 28 of the 47 (59.6%) asymptomatic SDHD mutation carriers. Risk of tumor development was significantly lower in SDHB mutation carriers: 2/17 (11.8%, P=0.001). Sympathetic paragangliomas were encountered in two SDHD mutation carriers and in one SDHB mutation carrier. In conclusion, asymptomatic carriers of an SDHD mutation are at a high risk for occult parasympathetic paraganglioma. SDHB carrier risk is considerably lower, consistent with lower penetrance of SDHB mutations. For both syndromes, the risk of symptomless sympathetic paragangliomas is small.
authors.affiliation: Department of Otolaryngology and ENT, LUMC, Leiden, The Netherlands.
authors.forename: Berdine L
authors.initials: BL
authors.lastname: Heesterman
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Bayley
authors.forename: Carli M
authors.initials: CM
authors.lastname: Tops
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
authors.forename: Bernadette T J
authors.initials: BT
authors.lastname: van Brussel
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: Jaap F
authors.initials: JF
authors.lastname: Hamming
authors.forename: Andel G L
authors.initials: AG
authors.lastname: van der Mey
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Jansen
mesh_terms: D058070:Asymptomatic Diseases; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase