Clinical Manifestations and Treatments of Patients With Tuberous Sclerosis With Subependymal Giant Cell Astrocytoma

This study aims to investigate the clinical and genetic characteristics of patients with tuberous sclerosis complex (TSC) with subependymal giant cell astrocytomas (SEGAs).

We conducted a retrospective study involving 263 patients with TSC, comparing clinical histories, genetic variants, and imaging data between patients with and without SEGAs. Additionally, we analyzed brain magnetic resonance imaging (MRI) findings of patients with TSC with SEGAs and evaluated the efficacy of everolimus in reducing SEGA volume.

SEGA was identified in 34 (12.9%) patients with TSC. The prevalence of pathogenic TSC2 variants was significantly higher in patients with SEGAs compared with those without SEGA. Patients with SEGAs also exhibited increased frequencies of retinal hamartomas, renal cysts, and hepatic angiomyolipomas. SEGAs were present in the initial brain imaging of 28 (82.4%) patients. Everolimus significantly reduced SEGA volume, with a median reduction of 33.7%. The most substantial reduction occurred during the first year of treatment, with a median decrease of 28.1%.

This study highlights that patients TSC with SEGAs are more likely to harbor pathogenic variants in the TSC2 gene and present with extracerebral manifestations of TSC, including retinal hamartomas, renal cysts, and hepatic angiomyolipomas. Most SEGAs were detectable from the initial brain imaging, suggesting that their presence can often be anticipated at the time of diagnosis. Everolimus proved effective and safe in significantly reducing SEGA volume during the first year of treatment in pediatric patients, although the rate of volume reduction decreased in subsequent years.