HGG-24. Concurrent Severe Spinocerebellar Ataxia and High-Grade Glioma: A Unique and Unreported Presentation

Abstract Spinocerebellar ataxias (SCAs) are a group of inherited neurodegenerative disorders characterized by progressive cerebellar dysfunction. Spinocerebellar ataxia type 10 (SCA10) is a rare SCA subtype that typically presents in early adulthood. SCA10 has no previously reported association with malignancy. This case report describes a patient with the previously undescribed concurrence of severe spinocerebellar ataxia and multifocal high-grade glioma (HGG). The patient initially presented at age 7 with an 8-month history of progressive neurological and cognitive decline, including right eye esotropia, dysphagia, facial palsy, and ataxia. Imaging revealed multifocal brain lesions involving the bilateral supratentorial and cerebellar regions. A biopsy of a left temporal lesion confirmed the presence of a high-grade neuroepithelial tumor, and molecular profiling identified MAPK-pathway activating mutations, including two separate NRAS mutations, an EGFR mutation, and a novel MN1::PAX7 fusion. Germline whole genome sequencing further revealed a heterozygous ATTCT full repeat expansion (1,000 repeats) in the ATXN10 gene, confirming SCA10. Given the lack of specific therapies for SCA, the patient received supportive interventions of physical, occupational, and speech therapy. For the HGG, targeted therapy with trametinib was initiated to avoid whole-brain radiation. However, after three months, progressive disease was noted and the patient underwent hypofractionated focal irradiation to progressive lesions, with radiographic improvement, followed by low-dose oral temozolomide. This case highlights the rare coexistence of severe SCA and HGG, emphasizing the importance of molecular profiling in guiding diagnosis and treatment. While no direct link between SCA and HGG has been reported, this case raises questions about the potential risk of brain malignancy in patients with SCA10.