MAX gene - Cancer risk, management, and testing for genetic mutations

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

MAX Summary Cancer Risk Table

Cancer Genetic Cancer Risk
EndocrineHigh Risk

MAX gene Overview

Hereditary pheochromocytoma-paraganglioma syndrome (hereditary PPGL syndrome) 1, 2, 3, 4, 5, 6, 7, 8, 9
  • Individuals with mutations in MAX have hereditary pheochromocytoma-paraganglioma syndrome (hereditary PPGL syndrome).
  • The MAX gene is believed to show a parent of origin effect. In most cases, only individuals who inherit the MAX gene mutation from their male parent are at increased risk to develop the disease manifestations associated with hereditary PPGL syndrome. When possible, genetic testing of parents may help predict the likelihood that this patient will be affected by hereditary PPGL syndrome. However, it is not yet certain that there is no risk when the MAX gene mutation is inherited from the female parent.
  • Individuals with hereditary PPGL syndrome due to mutations in MAX have a high risk for cancers of the nervous system (paragangliomas), which are most often in the abdomen, but can also be in the head, neck, or upper body. 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.
  • Some studies have shown that MAX mutations may also be associated with an increased risk for pituitary neuroendocrine tumors, parathyroid tumors, neuroblastoma, ganglioneuroma, lung cancer, and renal cancer. However, these studies are not conclusive and there are currently no medical management guidelines to address these possible risks.
  • Other genes associated with hereditary PPGL syndrome have an elevated risk for gastrointestinal stromal tumors (GIST). However, the data are not conclusive as to whether MAX mutations also cause an increased risk for these or other cancers at this time.
  • 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 National Comprehensive Cancer Network (NCCN), American Association for Cancer Research (AACR), and international consensus. These are summarized below. Since hereditary PPGL syndrome is a complex condition, and management recommendations are likely to change over time, individuals with MAX 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.

MAX gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Paraganglioma/PheochromocytomaTo age 40122%-50%, when paternally inherited<0.1%

MAX 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 measurement4, 610 to 15 yearsAnnually
Biochemical screening of blood and urine4, 610 to 15 yearsEvery 1 to 3 years, depending on symptoms and findings, or prior to any surgical procedure
Whole-body MRI. If not available, consider chest CT and MRI of abdomen, pelvis, skull base, and neck.4, 6, 910 to 15 yearsEvery 2 to 3 years

Benefits of Testing for MAX Gene Mutations:

Testing for MAX gene mutations with the MyRisk® Hereditary Cancer Test with RiskScore® provides critical insights to patients and providers about potential hereditary cancer risk. Identifying a MAX gene mutation can help clarify whether a patient is at increased risk for certain cancers and guide proactive, personalized care planning. With definitive answers from the MyRisk Test, healthcare providers can better tailor screening, prevention, and management strategies, while patients gain clarity and confidence about their hereditary cancer risk. In addition, understanding a MAX gene mutation allows family members to consider their own hereditary cancer risk, supporting informed decision-making and potentially life-saving early interventions. Learn more about the MyRisk® with RiskScore® Hereditary Cancer Test.

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 MAX 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 individuals with hereditary PPGL syndrome.5

The MAX gene is believed to show a parent of origin effect. In most cases, only children who inherit the MAX gene mutation from their male parent are at increased risk to develop the disease manifestations associated with hereditary PPGL syndrome. However, it is not yet certain that there is no risk when the MAX gene mutation is inherited from the female parent.2, 5, 7

Since paternally inherited MAX mutations carry a risk for complications in children and some screenings are recommended to begin as early as age 10 years, consideration should be given to mutation testing in childhood for offspring of male MAX mutation carriers. Offspring of female MAX mutation carriers may defer predictive testing until age 18, unless otherwise indicated based on family history.4, 5

References

  1. Bausch B, et al. Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. JAMA Oncol. 2017 Sep 1;3(9):1204-1212. PMID: 28384794.
  2. Burnichon N, et al. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res. 2012 May 15;18(10):2828-37. PMID: 22452945.
  3. Seabrook AJ, et al. Multiple Endocrine Tumors Associated with Germline MAX Mutations: Multiple Endocrine Neoplasia Type 5? J Clin Endocrinol Metab. 2021 Mar 25;106(4):1163-1182. PMID: 33367756.
  4. Casey RT, et al. International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents. Nat Rev Endocrinol. 2024 Aug 15. PMID: 39147856.
  5. Else T, et al. Hereditary Paraganglioma-Pheochromocytoma Syndromes. 2023 Sep 21. In: Adam MP, et al., editors. GeneReviews® [Internet]. PMID: 20301715.
  6. Bergsland E, et al. NCCN Clinical Practice Guidelines in Oncology®: Neuroendocrine and Adrenal Tumors. V 2.2025. May 28. Available at https://www.nccn.org.
  7. Chang X, et al. A Novel Phenotype of Germline Pathogenic Variants in MAX: Concurrence of Pheochromocytoma and Ganglioneuroma in a Chinese Family and Literature Review. Front Endocrinol (Lausanne). 2020 Aug 21;11:558. PMID: 32973681.
  8. Pantaleo MA, et al. Genome-Wide Analysis Identifies MEN1 and MAX Mutations and a Neuroendocrine-Like Molecular Heterogeneity in Quadruple WT GIST. Mol Cancer Res. 2017 May;15(5):553-562. PMID: 28130400.
  9. Greer MC, et al. Update on Whole-Body MRI Surveillance for Pediatric Cancer Predisposition Syndromes. Clin Cancer Res. 2024 Nov 15;30(22):5021-5033. PMID: 39287924.
Last Updated on 15-Sep-2025