Genetics Behind Pheochromocytoma and Paraganglioma

Inherited gene mutations are responsible for at least 20%-30% of all pheochromocytomas. Between 12% and 24% of patients with no obvious syndromes or family history associated with pheochromocytoma or paraganglioma appear to have mutations in one of the genes associated with the disease. To date, mutations in 6 genes have been identified to be responsible for familial pheochromocytomas or paragangliomas:

• von Hippel-Lindau (VHL) gene – tumor suppressor gene. Syndrome: VHL syndrome. About 10%-20% of patients with VHL disease develop pheochromocytoma
• RET gene – proto-oncogene. Syndrome: multiple endocrine neoplasia type 2 (MEN-2A or MEN-2B). Approximately 50% of patients with MEN-2 develop pheochromocytoma
• Neurofibromatosis type 1 (NF-1) gene – tumor suppressor gene. Syndrome: neurofibromatosis type 1. The risk of pheochromocytoma in this disorder is about 1%
• SDHB, SDHC, and SDHD genes – tumor suppressor genes. Syndrome: familial pheochromocytoma or paraganglioma. Mutations of SDHB and SDHD are associated with relatively high rates of paragangliomas compared with pheochromocytomas. Moreover, SDHB mutations are associated with more aggressive tumor behavior and a higher rate of malignancy