An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma

Best Pract Res Clin Endocrinol Metab. 2020 Mar;34(2):101416. doi: 10.1016/j.beem.2020.101416. Epub 2020 Mar 10.


Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumours characterized by a strong genetic determinism. Over the past 20 years, evolution of PPGL genetics has revealed that around 40% of PPGL are genetically determined, secondary to a germline mutation in one of more than twenty susceptibility genes reported so far. More than half of the mutations occur in one of the SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), which encode the different subunits and assembly protein of a mitochondrial enzyme, succinate dehydrogenase. These susceptibility genes predispose to early forms (VHL, RET, SDHD, EPAS1, DLST), syndromic (RET, VHL, EPAS1, NF1, FH), multiple (SDHD, TMEM127, MAX, DLST, MDH2, GOT2) or malignant (SDHB, FH, SLC25A11) PPGL. The discovery of a germline mutation in one of these genes changes the patient's follow-up and allows genetic screening of affected families and the presymptomatic follow-up of relatives carrying a mutation.

Keywords: SDHx; VHL; familial genetic screening; genetic; paraganglioma; pheochromocytoma.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis
  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / history
  • Adrenal Gland Neoplasms / pathology
  • DNA Mutational Analysis / history
  • DNA Mutational Analysis / trends
  • Genetic Association Studies / history
  • Genetic Association Studies / trends
  • Genetic Predisposition to Disease
  • Genetic Testing / history
  • Genetic Testing / methods
  • Genetic Testing / trends*
  • Germ-Line Mutation
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Mutation
  • Paraganglioma / diagnosis
  • Paraganglioma / genetics*
  • Paraganglioma / history
  • Paraganglioma / pathology
  • Pheochromocytoma / diagnosis
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / history
  • Pheochromocytoma / pathology
  • Succinate Dehydrogenase / genetics


  • SDHD protein, human
  • Succinate Dehydrogenase