The phenotype of SDHB germline mutation carriers: a nationwide study

• Published in: European journal of endocrinology Vol. 177; no. 2; pp. 115 - 125
• Main Authors: Niemeijer, Nicolasine D, Rijken, Johannes A, Eijkelenkamp, Karin, van der Horst-Schrivers, Anouk N A, Kerstens, Michiel N, Tops, Carli M J, van Berkel, Anouk, Timmers, Henri J L M, Kunst, Henricus P M, Leemans, C René, Bisschop, Peter H, Dreijerink, Koen M A, van Dooren, Marieke F, Bayley, Jean-Pierre, Pereira, Alberto M, Jansen, Jeroen C, Hes, Frederik J, Hensen, Erik F, Corssmit, Eleonora P M
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.08.2017; Oxford University Press
• Subjects: Adolescent; Adrenal Gland Neoplasms - diagnosis; Adrenal Gland Neoplasms - epidemiology; Adrenal Gland Neoplasms - genetics; Adult; Aged; Child; Clinical Study; Clonal deletion; Cohort Studies; Female; Follow-Up Studies; Gene deletion; Germ-Line Mutation - genetics; Head; Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - epidemiology; Head and Neck Neoplasms - genetics; Heterozygote; Hormone replacement therapy; Humans; Male; Metastases; Metastasis; Middle Aged; Mutation; Neck; Netherlands - epidemiology; Paraganglioma; Paraganglioma - diagnosis; Paraganglioma - epidemiology; Paraganglioma - genetics; Phenotype; Phenotypes; Pheochromocytoma; Pheochromocytoma - diagnosis; Pheochromocytoma - epidemiology; Pheochromocytoma - genetics; Pituitary; Renal cell carcinoma; Retrospective Studies; Statistical analysis; Succinate dehydrogenase; Succinate Dehydrogenase - genetics; Tumors; Young Adult
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-17-0074

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.