Targeted treatment for SHH+ Medulloblastoma in a pediatric patient with Gorlin Syndrome




Johnnidis, Melissa


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Background: We present a case of metastatic medulloblastoma (MB) of the sonic hedgehog (SHH) molecular subgroup in a patient with previously undiagnosed Gorlin syndrome who was subsequently treated with Vismodegib, a hedgehog signaling pathway inhibitor. A 4-year-old female presented with a 6-month history of worsening ataxia. Imaging revealed a mass which was determined to be MB following biopsy. Genetic testing identified a PTCH1 gene mutation, consistent with the diagnosis of Gorlin syndrome. Objectives: To describe a case of a patient with Gorlin syndrome and metastatic medulloblastoma treated with Vismodegib, a targeted therapy for the SHH molecular subgroup of the tumor. Design/Methods: A chart review was performed for this single case study. Results: The tumor was determined to be SHH+ MB. With the Gorlin syndrome diagnosis, radiotherapy (RT) was not recommended due to the increased risk of developing basal cell carcinomas, which are common in the disease. The tumor was resistant to chemotherapy, so she started Vismodegib. The drug was initially beneficial until months later when further metastases were found on imaging. Conclusion: Mainstay treatment of MB consists of a combined-modality approach utilizing RT, which is risky in Gorlin syndrome patients. The use of Vismodegib as targeted therapy in our patient seemed promising, but the tumor progressed. We present this case to raise awareness to the potential complications of treating MB in those with Gorlin syndrome. Multi-institutional studies are required to determine whether the drug should be given to patients with Gorlin syndrome and SHH+ MB.