Succinate dehydrogenase (SDHx) gene mutation

Last revised by Jan Czerminski on 9 Nov 2023

Succinate dehydrogenase gene (SDHx) germline mutations increase the risk of sympathetic paragangliomas, head and neck paragangliomas, pheochromocytomas, renal cell carcinoma (RCC), and gastric gastrointestinal stromal tumors (GIST) 1,2,6,7.


There are four SDH genes - SDHA, SDHB, SDHC, SDHD (collectively called SDHx) - which encode the four protein subunits of the SDH mitochondrial enzyme 6,7. In addition, SDHAF2 is needed for SDHA protein flavination 7.

In the citric acid cycle, SDH converts succinate to fumarate. Mutations in any one of the SDHx genes can result in mitochondrial dysfunction (SDH-deficiency) leading to neoplasia 6,7:

  • SDHA mutation

    • limited data

    • associated with SDH-deficient GIST

  • SDHB mutation

    • primarily retroperitoneal paraganglioma (more common) and pheochromocytoma

    • common in SDH-deficient RCC

    • highest risk of metastases

    • tumor risk in patients is probably <50% 5

  • SDHC mutation

    • limited data

    • primarily head and neck paragangliomas

    • common in SDH-deficient RCC

    • lower penetrance than SDHD mutation

  • SDHC epimutation (promotor hypermethylation)

    • associated with SDH-deficient GIST

  • SDHD mutation

    • primarily head and neck paragangliomas

    • highest penetrance


Treatment and prognosis

Asymptomatic SDHx carriers should undergo clinical and biochemical screening from childhood 6. MRI is recommended for childhood screening, and MRI and PET-CT recommended for adulthood screening 6.

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