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Eur J Endocrinol. 2017 Aug;177(2):115-125. doi: 10.1530/EJE-17-0074. Epub 2017 May 10.

The phenotype of SDHB germline mutation carriers: a nationwide study.

Author information

1
Department of Endocrinology and Metabolic DiseasesLeiden University Medical Center, Leiden, the Netherlands n.d.niemeijer@lumc.nl.
2
Department of Otorhinolaryngology/Head and Neck SurgeryVU University Medical Center, Amsterdam, the Netherlands.
3
Department of EndocrinologyUniversity of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
4
Department of Clinical GeneticsLeiden University Medical Center, Leiden, the Netherlands.
5
Division of EndocrinologyDepartment of Internal Medicine.
6
Department of Otorhinolaryngology/Head and Neck SurgeryRadboud University Medical Center, Nijmegen, the Netherlands.
7
Department of Endocrinology and MetabolismAcademic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
8
Department of Endocrine OncologyUniversity Medical Centre Utrecht, Utrecht, the Netherlands.
9
Department of Clinical GeneticsErasmus MC, University Medical Center, Rotterdam, the Netherlands.
10
Department of Human Genetics.
11
Department of Endocrinology and Metabolic DiseasesLeiden University Medical Center, Leiden, the Netherlands.
12
Department of OtorhinolaryngologyLeiden University Medical Center, Leiden, the Netherlands.

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.

PMID:
28490599
DOI:
10.1530/EJE-17-0074
[Indexed for MEDLINE]

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