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Fatal brainstem injury following proton radiation in a patient with medulloblastoma and a germline variant in RNF213
Darren M Klawinski1, Catherine E Cottrell2, Kathleen M Schieffer2
1Department of Pediatrics, Nemours Children's Health Jacksonville, Jacksonville, Florida, USA.
Insights
Pediatric brainstem injury from radiation can be fatal, occurring years later. A specific RNF213 gene variant may increase risk for radiation necrosis in children.
Area of Science:
- Neuro-oncology
- Radiation oncology
- Genetics
Background:
- Posterior fossa radiation therapy is used for pediatric brain tumors.
- Brainstem injury is a known complication, occurring months to years post-treatment.
- Risk factors include young age (<5 years) and comorbidities like cerebrovascular disease.
Observation:
- Radiation necrosis of the brainstem can be symptomatic and fatal.
- A pathogenic variant in the RNF213 gene was identified in a patient with fatal radiation necrosis.
- This RNF213 mutation is linked to moyamoya disease.
Findings:
- The RNF213 pathogenic variant may predispose pediatric patients to developing radiation necrosis.
- This genetic factor could explain susceptibility in certain individuals post-radiation.
Implications:
- Identifying patients with RNF213 variants could allow for personalized risk assessment and monitoring.
- Further research into RNF213's role in radiation sensitivity is warranted.
- This finding may inform future treatment strategies to mitigate brainstem injury risk.
Abstract:
Brainstem injury occurs secondary to radiation to the posterior fossa in up to 2% of pediatric patients. It may occur after months to years after treatment. It has been associated with age less than 5 years and with comorbid conditions such as cerebrovascular disease, diabetes mellitus, and hypertension. Radiation necrosis is often symptomatic and can be fatal. A pathogenic variant in RNF213 was found in a patient who suffered fatal radiation necrosis. This mutation has been associated with moyamoya disease and may predispose to radiation necrosis.
