aetiology

Last reviewed 07/2023

The aetiology is not known but a significant genetic component is recognised. Ten percent are familial. These are invariably adrenal in origin, and are bilateral in 70%.

  • majority arise sporadically
  • 25-30% caused by germline mutations in one of the five phaeochromocytoma susceptibility genes
  • inherited either as:
    • autosomal dominant trait
    • MEN II syndrome (RET gene)
    • Von Hippel-Lindau disease (VHL gene)
    • neurofibromatosis Type 1 (NF1 gene) - in 5% of cases of phaeochromocytoma
    • familial pheochromocytoma-paraganglioma syndrome (SDHD/B and C genes)
  • about 120 variants of SDHD/B and C genes (succinate dehydrogenase genes) have been isolated
  • tumor suppressor genes : when deactivated the transcription factor hypoxia-inducible factor (HIF) is activated
  • HIF-1 and HIF-2 have been implicated in VHL, SDHB, and SDHD mutations

Reference:

  1. Gimenez-roqueplo A-P. New advances in the genetics of pheochromocytoma and paraganglioma syndromes. Ann. N.Y. Acad. Sci 2006; 1073: 112 - 121.
  2. Korpershoek E et al.Genetic analyses of apparently sporadic pheochromocytomas: the rotterdam experience. Ann. N.Y. Acad. Sci 2006; 1073: 138 - 148.

Related pages:

MEN-IIa

MEN-IIb

neurofibromatosis

von Hippel-Lindau syndrome

tuberous sclerosis