SDHB gene

Associated Syndrome Name: Hereditary pheochromocytoma-paraganglioma syndrome (hereditary PPGL syndrome)

SDHB Summary Cancer Risk Table

Cancer Genetic Cancer Risk
EndocrineHigh Risk
OtherElevated Risk
RenalElevated Risk

SDHB gene Overview

Hereditary pheochromocytoma-paraganglioma syndrome (hereditary PPGL syndrome) 1, 2, 3, 4, 5, 6
  • Individuals with mutations in SDHB have hereditary pheochromocytoma-paraganglioma syndrome (hereditary PPGL syndrome).
  • Individuals with hereditary PPGL syndrome due to mutations in SDHB have a high risk for cancers of the nervous system (paragangliomas), which can be in the head, neck, upper body or abdomen. There is also a high risk for paragangliomas of the adrenal gland (pheochromocytomas). Paragangliomas and pheochromocytomas can develop at young ages.
  • Paragangliomas and pheochromocytomas in individuals with hereditary PPGL syndrome often secrete hormones that can cause symptoms such as high blood pressure, rapid and/or abnormal heartbeat, headaches, sweating, nausea, fatigue and anxiety.
  • Individuals with hereditary PPGL syndrome due to SDHB mutations have an elevated risk for renal cancer and for gastrointestinal stromal tumors (GIST), mostly in the stomach.
  • Some studies have shown that hereditary PPGL syndrome also includes an increased risk for pituitary adenomas and neuroblastoma. However, the data are not conclusive at this time and there are currently no specific medical management guidelines related to any of these other tumors.
  • It is appropriate to offer genetic counseling to individuals with hereditary PPGL syndrome who are of reproductive age to discuss reproductive risks and options. There are additional considerations before and during pregnancy for women with hereditary PPGL syndrome.
  • Although there are high risks for cancers and other medical conditions in individuals with hereditary PPGL syndrome, it may be possible to reduce these risks with appropriate medical management. Guidelines for the medical management of patients with hereditary PPGL syndrome have been developed by the American Association for Cancer Research (AACR) and the National Comprehensive Cancer Network (NCCN). These are summarized below. Since hereditary PPGL syndrome is a complex condition, and management recommendations are likely to change over time, patients with SDHB mutations and a diagnosis of hereditary PPGL syndrome should be managed by a multidisciplinary team with expertise in medical genetics and the prevention and treatment of the complications associated with this condition.

SDHB gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Paraganglioma/PheochromocytomaTo age 601, 3, 5, 6, 725%<0.1%
RenalTo age 603, 4, 6, 74%-5%0.5%
Gastrointestinal Stromal Tumors (GIST)To age 803, 6, 72%<0.1%

SDHB Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
Paraganglioma/PheochromocytomaClinical monitoring, including blood pressure measurement2, 5, 86 to 10 yearsAnnually
Biochemical screening of serum and urine2, 5, 86 to 10 yearsEvery 1 to 2 years
Whole-body MRI with consideration of the head and neck2, 5, 86 to 10 yearsEvery 2 to 3 years
RenalAbdominal MRI (preferred) or CT, with and without IV contrast412 yearsEvery 4 to 6 years
Gastrointestinal Stromal Tumors (GIST)Complete blood count and attention to symptoms such as gastric bleeding, obstruction, abdominal pain, nausea, etc.26 to 8 yearsAnnually

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the SDHB gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

It is appropriate to offer genetic counseling to individuals with hereditary PPGL syndrome who are of reproductive age to discuss reproductive risks and options. There are additional considerations before and during pregnancy for women with hereditary PPGL syndrome.6

Since SDHB mutations carry a risk for complications in children and some screenings are recommended to begin as early as age 6 years, consideration should be given to mutation testing in childhood.2

In rare instances, an individual may inherit mutations in both copies of the SDHB gene, leading to mitochondrial disease (such as mitochondrial complex II deficiency). These conditions are rare and symptoms can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. The children of this patient are at risk of inheriting these conditions only if the other parent is also a carrier of an SDHB mutation. A child of this patient may be at risk for these conditions even if the other parent does not yet have a diagnosis of hereditary PPGL syndrome. Screening the other biological parent of any children for SDHB mutations may be appropriate.9

References

  1. Jochmanova I, et al. Clinical chracteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. J Cancer Res Clin Oncol. 2020 146:1051-1063. PMID: 32062700.
  2. Rednam SP, et al. Von Hippel-Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res. 2017 23:e68-e75. PMID: 28620007.
  3. Andrews KA, et al. Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. J Med Genet. 2018 55:384-394. PMID: 29386252.
  4. Motzer RJ et al. NCCN Clinical Practice Guidelines in Oncology®: Kidney Cancer. V 4.2023. Jan 18. Available at https://www.nccn.org.
  5. Bergsland E, et al. NCCN Clinical Practice Guidelines in Oncology®: Neuroendocrine and Adrenal Tumors. V 2.2022. Dec 21. Available at https://www.nccn.org.
  6. Else T, et al. Hereditary Paraganglioma-Pheochromocytoma Syndromes. 2008 May 21 [updated 2018 Oct 4]. In: Adam MP, et al., editors. GeneReviews® [Internet]. PMID: 20301715.
  7. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2023 Mar 24]. Available from https://seer.cancer.gov/explorer/.
  8. Amar L, et al. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nat Rev Endocrinol. 2021 17(7):435-444. PMID: 34021277.
  9. Alston CL, et al. Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. J Med Genet. 2012 49:569-77. PMID: 22972948.
Last Updated on 31-Jan-2024