Approximately one third of unselected individuals with phaeochromocytoma and/or paraganglioma have a germline mutation in one of the 6 main genes (VHL, RET, NF1, SDHB, SDHD and SDHC). Mutations are identified in 11-18% of individuals with apparently sporadic presentation and 40-70% with a family history.
Germline mutations in SDHAF2, TMEM127, MAX and SDHA have been reported in both apparently sporadic and familial phaeochromocytoma and/or paraganglioma. The prevalence of mutations in these genes is low, but poorly defined.rr
The rate of de novo mutations is currently unknown.
||Probability of detecting a heritable mutationrr
|Age of onset
||SDHB > SDHD > VHL > RET#
||SDHB/VHL > SDHD
|VHL > RET > SDHB/D
|Single head and neck paraganglioma*
||SDHD > SDHB/C > VHL
|Single thoracic or retroperitoneal paraganglioma**
|SDHB > SDHD/C
|Paraganglioma/phaeochromocytoma at multiple sites***
||VHL > RET/SDHB
||SDHB > VHL > SDHD
||Up to 87%
||SDHB > SDHD/VHL
|Patient has a first or second degree relative with documented pathogenic mutation
||89% of all SDH mutations are due to 6 founder mutations
#In this section of the table the >symbol is utilised to represent more likely than
*Reported series are all clinic based and are affected by specific effects of ascertainment. Population based estimates are not currently available.
**Excludes unilateral adrenal phaeochromocytoma
***Includes bilateral adrenal phaeochromocytoma
Note: It is often difficult to compare mutation pick up by clinical phenotype across different study cohorts; some studies excluded patients with syndromic features of VHL, NF1 or MEN2 others did not; some excluded a family history of paraganglioma whilst others did not; some used the WHO classification for paraganglioma/phaeochromocytoma, others did not.
For further references used to develop this table please see the History icon.