A novel pathogenic variant in MAX-Associated pheochromocytoma

Abstract

Objective: To describe a young woman with malignant pheochromocytoma related to a relatively novel pathogenic variant of MAX gene and to compare to previous case reports on MAX pathogenic variants. Case report: A 19-year-old patient with a history of norepinephrine-secreting pheochromocytoma resected at age 11 presented to our clinic with symptoms and biochemical evaluation concerning for recurrence. After confirmation of recurrence, 3 metastatic lymph nodes were successfully resected. Genetic testing disclosed a pathogenic germline MAX variant c.22G > T. Her sister and father were found to harbor the same variant, but her paternal grandparents did not. Her sister had a baseline MRI and plasma metanephrines that were both normal. Discussion: As whole gene panels are used more frequently for evaluation of hereditary pheochromocytomas, it is important to understand the different clinical phenotypes and natural histories that can be associated with each MAX variant. Our patient presented at a younger age than any other MAX-associated pheochromocytoma, possibly due to her variant translating an early stop codon and encoding a more dysfunctional protein. Available case reports suggest that 98% of MAX-associated pheochromocytomas are functional, which may inform screening procedures. Conclusion: Clinicians should be aware of MAX-associated pheochromocytomas and how they may differ from other hereditary pheochromocytoma syndromes. For asymptomatic individuals with a MAX pathogenic variant, screening with plasma metanephrines without imaging may be a cost-effective and patient-centered approach.

Keywords

• Pheochromocytoma
• Gene
• Variant
• Paraganglioma
• MAX