Most pediatric paragangliomas, rare tumors that develop in the head, neck, or torso, are linked to inherited genetic mutations, highlighting the critical need for genetic testing to personalize treatment and assess the risk of metastasis. While these tumors are uncommon, understanding their genetic drivers is increasingly recognized as essential for optimal patient care.
A physician at the University of Miami Miller School of Medicine is advocating for a shift in how these tumors are managed. Simon Angeli, M.D., a professor of otolaryngology—head and neck surgery and neurosurgery and director of the UHealth Ear Institute, recently presented compelling evidence at the North American Skull Base Society meeting in San Diego, arguing that genetic testing should be standard practice from the moment of diagnosis, particularly in children.
The Genetic Basis of Pediatric Paragangliomas
Paragangliomas arise from specialized cells of the autonomic nervous system. In the head and neck, they typically occur near major blood vessels like the carotid artery and cranial nerves. They can also develop in the torso, often in the adrenal glands or mediastinum. Researchers have identified mutations in approximately a dozen genes associated with an increased risk of developing these tumors. A study of 55 pediatric patients revealed that around 80 percent carried heritable mutations known to drive paraganglioma development, with changes in the SDHB and VHL genes being the most frequently observed, according to the presentation by Dr. Angeli.
“By doing genetic testing, you’re personalizing the management by giving each individual patient the appropriate treatment for his or her tumor,” Dr. Angeli explained. “You don’t overtreat patients that don’t need the tumor removed, and you can treat aggressively those with a high risk of metastatic disease.”
Predicting Metastatic Risk Through Genetic Testing
While paragangliomas are not typically classified as cancerous, they can, in some cases, metastasize—spread to other parts of the body. Identifying specific genetic mutations can help clinicians predict the likelihood of metastasis and tailor treatment accordingly. Mutations in the SDHB gene, part of the succinate dehydrogenase complex, are particularly concerning, as they carry a significantly elevated risk of metastatic disease.
“When we identify those mutations, we tend to be more proactive in terms of surgery,” Dr. Angeli stated. Defects in other subunits of the succinate dehydrogenase complex generally indicate a less aggressive disease course.
Although, Dr. Angeli cautioned that current understanding of hereditary paragangliomas is largely based on studies conducted on European and North American populations. He emphasized the importance of considering ethnic differences, as his team’s recent investigations have shown that paragangliomas in South Florida Hispanics exhibit a different genetic profile and behavior compared to those reported in other populations.
Implications for Family Members and Long-Term Care
The implications of genetic testing extend beyond the individual patient. Dr. Angeli routinely offers testing to first-degree relatives, who may unknowingly carry the same mutation. Early detection through genetic screening can lead to earlier intervention and potentially less invasive treatment options. “Then you’re done with it, without waiting for the tumor to grow, and for the patient to need a bigger surgery and with more risks,” he said.
A mutation in the VHL gene, associated with Von Hippel-Lindau disease, presents a unique challenge. This mutation indicates a potential for tumors to develop in other parts of the body, even in the absence of symptoms.
While genetic testing for paragangliomas has been available for several years, its adoption has been inconsistent. Dr. Angeli believes that increased awareness of the benefits of genetic testing will lead to more widespread use and improved patient outcomes. “It’s been around for five to 10 years, but not everybody is using it,” he noted. “The advantages of knowing this information about a tumor before offering treatment are becoming more and more evident.”
Disclaimer: This information is intended for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
As research continues to unravel the genetic complexities of paragangliomas, the hope is that increasingly precise and personalized treatment strategies will emerge, ultimately improving the lives of children and families affected by these rare tumors. Further studies are needed to refine risk stratification and optimize surveillance protocols based on genetic profiles.
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