title: Phenotype of SDHB mutation carriers in the Netherlands.
abstract: SDHB mutation carriers are predisposed to developing paragangliomas (PGLs). The objective of this study was to assess genotype-phenotype correlations of a Dutch cohort of SDHB mutation carriers and assess potential differences in clinical phenotypes related to specific SDHB founder mutations. Forty-seven consecutive SDHB mutation carriers were included. Initial screening consisted of measurement of 24 h urinary excretion of catecholamines and their metabolites in duplicate, repeated annually if initial biochemical screening was negative. Whole-body imaging studies with magnetic resonance imaging (MRI) or computed tomography (CT) and/or (123)I-MIBG scintigraphy were performed in case of catecholamine excess, and MRI or CT scans of thorax, abdomen and pelvis were performed every 2 years regardless of catecholamine levels. Repetitive head-and-neck MRI was performed at 2 year intervals. Mean follow-up was 3.6 ± 3.6 years. Twenty-seven persons (57 %) carried the SDHB c.423+1 G>A mutation and seven persons (15 %) the SDHB c.201-4429_287-933del (exon 3 deletion) mutation. No differences were found in the clinical phenotype of carriers of these two specific SDHB mutations. By end of follow-up, 49 % of SDHB mutation carriers displayed no biochemical or radiological evidence of manifest disease, i.e. they were unaffected carriers. Three persons (6 %) had been diagnosed with a pheochromocytoma (PCC), four with a sympathetic PGL (sPGL) (9 %), 18 with a HNPGL (38 %), and two persons (4 %) had developed a malignant paraganglioma, i.e. metastatic disease. In conclusion, the two main Dutch SDHB founder mutations do not differ in clinical expression and result in a relatively mild phenotype. Over one-third of SDHB mutation carriers develop HNPGL, with sPGL/PCC in only 15 % and malignancy in only 4 %.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands, L.T.van_Hulsteijn@lumc.nl.
authors.forename: Leonie T
authors.initials: LT
authors.lastname: van Hulsteijn
authors.forename: Nienke D
authors.initials: ND
authors.lastname: Niemeijer
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bayley
authors.forename: Carli M
authors.initials: CM
authors.lastname: Tops
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Jansen
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
mesh_terms: D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009426:Netherlands; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: C108095:SDHB protein, human; D013385:Succinate Dehydrogenase