Aetiology

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.