Diffuse hemispheric glioma, H3 G34-mutant, in Simpson-Golabi-Behmel syndrome: the first reported case

Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome associated with an increased risk of certain malignancies; however, gliomas have not previously been reported in patients with SGBS. Loss-of-function variants in glypican-3 (GPC3) represent the primary molecular mechanism underlying SGBS-related overgrowth and tumorigenesis, although their relationship with gliomas remains unclear. We report a case of an 18-year-old male who had been clinically diagnosed with Sotos syndrome in childhood. He presented with sudden impaired consciousness, and neuroimaging revealed a large tumor in the left occipitoparietal lobe, which was subsequently resected. Histopathological analysis demonstrated a pediatric-type diffuse hemispheric glioma, H3 G34-mutant (CNS WHO grade 4). Next-generation sequencing of peripheral blood DNA identified a germline hemizygous deletion encompassing exons 3-5 of GPC3, leading to a revised diagnosis of SGBS. To our knowledge, this is the first reported case of SGBS associated with a glioma. This case raises the possibility that GPC3 alterations may contribute to gliomagenesis, including in H3 G34-mutant diffuse hemispheric glioma.