Objective: SDHD mutations predispose carriers to hereditary paraganglioma syndrome. The objective of this study was to assess the genotype-phenotype correlation of a large Dutch cohort of SDHD mutation carriers and evaluate potential differences in clinical phenotypes due to specific SDHD gene mutations.
Design: Retrospective, descriptive single-centre study.
Patients: All consecutive SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center were included.
Measurements: Subjects were investigated according to structured protocols used for standard care, including repetitive biochemical and radiological screening for paragangliomas.
Results: Two hundred and one SDHD mutation carriers with a mean age at presentation of 42·6 ± 14·4 years and a mean follow-up of 5·8 ± 5·4 years were evaluated. Eighty-one percent carried the SDHD c.274G>T (p.Asp92Tyr) mutation and 13% the SDHD c.416T>C (p.Leu139Pro) mutation. No differences in clinical phenotype between these two specific SDHD mutations were found. Ninety-one percent developed one or multiple paragangliomas in the head and neck region (HNPGLs), of which the carotid body tumour was the most prevalent (85%). Eighteen carriers developed pheochromocytomas, fifteen sympathetic paragangliomas and nine carriers (4%) suffered from malignant paraganglioma. By end of follow-up, sixteen SDHD mutation carriers (8%) displayed no biochemical or radiological evidence of manifest disease.
Conclusions: The two main Dutch SDHD founder mutations do not differ in clinical expression. SDHD mutations are associated with the development of multiple HNPGLs and predominantly benign disease.
© 2013 John Wiley & Sons Ltd.