SDHA gene

Associated Syndrome Name: Hereditary Pheochromocytoma-Paraganglioma syndrome (Hereditary PPGL syndrome)

SDHA Summary Cancer Risk Table

Cancer Genetic Cancer Risk
EndocrineHigh Risk
OtherElevated Risk
RenalElevated Risk

SDHA gene Overview

Hereditary Pheochromocytoma-Paraganglioma syndrome (Hereditary PPGL syndrome) 1, 2, 3, 4, 5, 6
  • Individuals with mutations in SDHA have Hereditary Pheochromocytoma-Paraganglioma syndrome (Hereditary PPGL syndrome).
  • Individuals with Hereditary PPGL syndrome due to mutations in SDHA have a high risk for benign and malignant tumors 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. In individuals with an SDHA mutation, most of these tumors are benign, but there is some risk for them to become malignant (cancerous) and spread to other parts of the body.
  • Individuals with Hereditary PPGL syndrome due to SDHA mutations have an elevated risk for renal cancer and for gastrointestinal stromal tumors (GIST), mostly in the stomach. The exact level of these risks is not known.
  • Some studies have shown that Hereditary PPGL syndrome also includes an increased risk for other tumors and cancers, such as pituitary adenomas and neuroblastoma. However, the data are not conclusive at this time and there are currently no specific medical management guidelines related to 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 during pregnancy for women with Hereditary PPGL syndrome.
  • Although there are high risks for tumors 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 SDHA 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.

SDHA gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Paraganglioma/PheochromocytomaTo age 703, 4, 6, 710% risk for tumors, only some of which will be malignant<0.1%
RenalTo age 806, 7, 8Elevated risk1.4%
Gastrointestinal Stromal Tumors (GIST)To age 802, 3, 4, 7Elevated risk<0.1%

SDHA 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 measurement1, 26 to 8 yearsAnnually
Biochemical screening of serum and urine1, 26 to 8 yearsAnnually
Whole-body MRI with consideration of the head and neck1, 26 to 8 yearsEvery 2 years
RenalAbdominal MRI (preferred) or CT, with and without IV contrast812 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 SDHA 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 during pregnancy for women with Hereditary PPGL syndrome.3

Since SDHA 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 SDHA 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 SDHA 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 SDHA mutations may be appropriate.9

References

  1. Shah MH, et al. NCCN Clinical Practice Guidelines in Oncology®: Neuroendocrine and Adrenal Tumors. V 2.2021. June 18. Available at https://www.nccn.org.
  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. 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.
  4. Fishbein L. Pheochromocytoma/Paraganglioma: Is This a Genetic Disorder? Curr Cardiol Rep. 2019 21:104. PMID: 31367972.
  5. Dubard Gault M, et al. Germline SDHA mutations in children and adults with cancer. Cold Spring Harb Mol Case Stud. 2018 4: PMID: 30068732.
  6. van der Tuin K, et al. Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study. J Clin Endocrinol Metab. 2018 103:438-445. PMID: 29177515.
  7. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from https://seer.cancer.gov/explorer/.
  8. Motzer RJ et al. NCCN Clinical Practice Guidelines in Oncology®: Kidney Cancer. V 1.2022. July 1. Available at https://www.nccn.org.
  9. Renkema GH, et al. SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Eur J Hum Genet. 2015 23:202-9. PMID: 24781757.
Last Updated on 21-Apr-2022