Cerebral hyaline astrocytic inclusions (HAI) have been observed in a subset of patients with epilepsy, structural brain anomalies, and developmental delay. We present a case of a 2.5-year-old male with epilepsy and global developmental delay. Chromosomal microarray detected a copy loss at 22q13 that resulted in a partial deletion of SHANK3 gene. The EEGs revealed seizure activity arising from left frontal central region. Invasive video electrocorticography captured clusters of epileptic spasms, all originating from left antero-lateral frontal lobe rostral to the motor cortex. We utilized routine histology to identify the inclusions and mapped their distribution in the resected portion of the cortex against electrocorticographic data. Histologic analysis revealed the presence of HAI in the posterio-medial portion of the resected cortex, which corresponded to the site of seizure generalization. HAI were present at the resection margin. Immunohistochemistry was largely non-contributory. HAI is a rare but emerging entity that is associated with epilepsy. To our knowledge, the distribution of inclusions in HAI has never been mapped to electrophysiologic data. In our case, seizure generalization correlated with the inclusions distribution. This suggests that the inclusions may: 1) play a role in epileptogenesis; or, 2) be a biomarker of disease distribution. Finally, the presence of the HAI at the resection margin may foreshadow future seizure activity in this patient.