Pathogenic variants (disease-causing) in the MAX gene can predispose individuals to tumors such as paragangliomas (head and neck tumor) and pheochromocytomas (adrenal gland tumor). Management of MAX–related tumor risk includes regular surveillance tailored to guidelines for hereditary paraganglioma–pheochromocytoma syndromes, typically involving periodic biochemical testing, whole-body or targeted MRI, and clinical evaluation to detect tumors early. MAX variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in MAX exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family. However, a unique feature of the MAX gene is called a ‘parent-of-origin effect’, meaning that increased tumor risk is seen almost exclusively when the pathogenic variant is inherited from the father, not the mother.
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Written December 2025
