The Genetic Component

Up to about 24% of patients with pheochromocytoma or paraganglioma will have a family member with the same condition. Inherited mutations in 6 genes have been found to be responsible for the condition. These genes include:

• von Hippel-Lindau (VHL) gene

  Mutation in this gene may cause VHL syndrome. About 10%-20% of patients with VHL syndrome develop pheochromocytoma

• RET gene

  Mutation in this gene may cause 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

  Mutation in this gene may cause neurofibromatosis type 1. The risk of pheochromocytoma in patients with NF-1 is about 1%

• SDHB, SDHC, and SDHD genes

  Mutation in these genes may cause 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

Genetic testing is recommended for most patients with pheochromocytoma or paraganglioma. Once a specific mutation is found, stepwise family testing is advised (eg, parents first). When relatives are found to have the mutation, additional testing is indicated to determine whether pheochromocytoma or paraganglioma is present.