Rare single gene disorders manifest in the neonatal period. The Next Generation Children's Project has used whole genome sequencing of patients and their parents to diagnose 50 patients with neurogenetic epilepsy syndromes. For example, Kv7.2 voltage-gated potassium channel subunit dysfunction is associated with KCNQ2 mutations, with resulting increased network excitability. It is increasingly clear that epilepsy-causing gene mutations affect the major glial cell populations, principally astrocytes, rather than neurons. To date, human induced pluripotent stem cell-derived (iPSC) neurons have been generated with epilepsy-causing potassium/sodium channel mutations and gene deletions, however, lack the ability to establish human cortical connections. The development of human three-dimensional cerebral organoid models (CO) that incorporate circuit forming neuron and glial phenotypes present a unique opportunity to develop new approaches in precision medicine for paediatric epilepsy patients. This project aims to generate CO from CRISPR/Cas9 KCNQ2 and KCNJ10-edited H9 ECS lines and from patient-derived iPSC-line. To assess if stem cell-derived CO harbouring KCNQ2 or KCNJ10 mutations show altered cortical plate development, assessing CO cell composition by immunolabeling for cell type-specific markers (GAD2/ CTIP2+). To show whether CO slices with perturbed KCNQ2 and KCNJ10 function or expression show bursts in activity and whether this can be suppressed by Na+ or K+ channel drugs.