The phenotype of SDHB germline mutation carriers: A nationwide study

Nicolasine D. Niemeijer*, Johannes A. Rijken, Karin Eijkelenkamp, Anouk N.A. Van Der Horst-Schrivers, Michiel N. Kerstens, Carli M.J. Tops, Anouk Van Berkel, Henri J.L.M. Timmers, Henricus P.M. Kunst, C. René Leemans, Peter H. Bisschop, Koen M.A. Dreijerink, Marieke F. Van Dooren, Jean Pierre Bayley, Alberto M. Pereira, Jeroen C. Jansen, Frederik J. Hes, Erik F. Hensen, Eleonora P.M. Corssmit

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: Succinate dehydrogenase B subunit (SDHB) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of SDHB germline mutation carriers and assess differences in clinical phenotypes related to specific SDHB mutations. Design: Retrospective descriptive study. Methods: Retrospective descriptive study in seven academic centers. Results: We included 194 SDHB mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%) relatives. Mean age was 44.8 ± 16.0 years. Median duration of follow-up was 2.6 years (range: 0-36). Sixty persons (30.9%) carried the exon 3 deletion and 46 (23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26 (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%) developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic tumors. At study close, there were 111 (57.2%) unaffected mutation carriers. Statistical analyses showed no significant differences in the number and location of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas, nor in the occurrence of metastatic disease or other tumors between carriers of the two founder SDHB mutations (exon 3 deletion vs c.423 + 1G > A). Conclusions: In this nationwide study of disease-affected and unaffected SDHB mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalEuropean Journal of Endocrinology
Volume177
Issue number2
DOIs
Publication statusPublished - 1 Aug 2017

Cite this

Niemeijer, N. D., Rijken, J. A., Eijkelenkamp, K., Van Der Horst-Schrivers, A. N. A., Kerstens, M. N., Tops, C. M. J., ... Corssmit, E. P. M. (2017). The phenotype of SDHB germline mutation carriers: A nationwide study. European Journal of Endocrinology, 177(2), 115-125. https://doi.org/10.1530/EJE-17-0074