Hereditary paragangliomas

Adv Otorhinolaryngol. 2011:70:99-106. doi: 10.1159/000322484. Epub 2011 Feb 24.


Paragangliomas (PGL) and pheochromocytomas (PCC) are rare, usually benign tumors that originate from the neuroendocrine tissue along the paravertebral axis. Up to 35% of these tumors may be hereditary; they are associated with germline mutations in genes encoding subunits of the succinate dehydrogenase (SDH) enzyme complex in the context of the familial PGL syndromes, PGL1, 3 and 4 caused by mutations in the SDHD,SDHC and SDHB genes, respectively. Another familial PGL syndrome, PGL2, is caused by mutations in SDHAF2/SDH5, which encodes for a molecule that is an accessory to the function of the SDH enzyme and its SDHA subunit. Less frequently, mutations in the genes responsible for Von Hippel Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis type 1 (NF1) are also found in patients with hereditary PGL and PCC. Recently mutations were found in the SDHA subunit in a limited number of patients with PGL and/or PCC. The SDHB, SDHC and SDHD gene mutations (but not SDHA) can also be found in patients with PGL and/or PCC and gastrointestinal stromal tumors (GISTs), also known as the Carney-Stratakis syndrome; SDHB mutations, in particular, may also predispose to thyroid and renal cancer, and possibly other tumors. A new gene was recently found to predispose to PGL and/or PCC when mutated is TMEM127. In this text, we provide an overview of the genetics of PGLs and related conditions with an emphasis on genetic risk assessment, prevention, and prognosis.

Publication types

  • Review

MeSH terms

  • Genetic Predisposition to Disease
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Neurofibromatosis 1 / genetics
  • Paraganglioma / genetics*
  • Prevalence
  • Prognosis
  • Risk Assessment
  • Succinate Dehydrogenase / genetics*
  • Syndrome
  • von Hippel-Lindau Disease / genetics


  • Succinate Dehydrogenase