No difference in phenotype of the main Dutch SDHD founder mutations

Clin Endocrinol (Oxf). 2013 Dec;79(6):824-31. doi: 10.1111/cen.12223. Epub 2013 May 11.


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.

MeSH terms

  • Adrenal Gland Neoplasms / genetics
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Founder Effect*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Head and Neck Neoplasms / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplastic Syndromes, Hereditary / enzymology*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Netherlands
  • Paraganglioma / enzymology*
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics
  • Retrospective Studies
  • Succinate Dehydrogenase / genetics*
  • Young Adult


  • SDHD protein, human
  • Succinate Dehydrogenase