J Neurol Surg B Skull Base 2016; 77 - FP-22-02
DOI: 10.1055/s-0036-1592549

Phenotype and Penetrance of the Dutch SDHB Mutation Carriers

Johannes A. Rijken 1, Nienke D. Niemeijer 2, Anouk N.A. van der Horst-Schrivers 3, Eleonora P. Corssmit 2, Erik F. Hensen 1
  • 1Department of Otolaryngology, Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
  • 2Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
  • 3Department of Endocrinology and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands

Objectives: Nationwide evaluation of the phenotype and penetrance of SDHB mutation carriers.

Methods: Mutations in SDHB predispose to skull base paragangliomas. In a nationwide study, all consecutive SDHB mutation carriers identified in the clinical genetics centers of the Netherlands were included in the analysis. Subjects were investigated according to structured protocols used for standard care in the Netherlands, including repetitive physical, biochemical and radiological screening for paraganglioma (PGL) and pheochromocytoma (PCC).

Results: A total of 194 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The most prevalent SDHB mutations are Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). In all, 93 tumors (PGL and PCC) were identified in 80 patients. 55 patients (28%) had a head and neck PGL, in total 63 tumors. 4 patients had a PCC (2%), 22 patients (11%) an extra-adrenal PGL (total 26 tumors) and 12 patients (6%) a malignant PGL. 114 SDHB mutation carriers displayed no physical, radiological or biochemical evidence of PGL or PCC.

Conclusion: In the Netherlands, SDHB mutations are an infrequent finding. Carriers of SDHB mutations have a considerable risk of developing a PGL. Contrary to most previous reports, the most prevalent PGL location is in the head and neck region, abdominal and thoracic tumors are uncommon and malignancy is rare.