Clinical features of three probands. A1, A2: MRIs for case 1 at 8months. MRI revealed widened subdural space of bilateral frontal and temporal, and slightly expanded ventricular system. B1, B2: Normal MRI for case 2 at 2 years and 2 months. MRI revealed slightly wider at subarachnoid space of the temporal pole. C1, C2: MRI for case 3 at 1 years and 1months. MRI revealed slightly wider at subarachnoid space of the frontal and temporal pole. D: Typical hypsarrhythmia EEG

Disruption of Zebrafish irf2bpl Leads to Spontaneous Seizures. A. Representative bright-field imaging of larval zebrafish at 5 days post fertilization (dpf). Top, cas9 injected control; bottom, irf2bpl F0 CRISPR (crispant). B-C. Measurements of eye distance and body length in cas9 injected control (n = 20 fish) vs. irf2bpl crispants (n = 26 fish; unpaired t test). Data were normalized to the average values of cas9 control group. D. Representative imaging of HuC: eGFP expressed larval zebrafish shows CNS fluorescence pattern at 5 dpf (dorsal view). Left, cas9 injected control; right, irf2bpl crispant. E. Normalized CNS area in cas9 injected controls vs. irf2bpl crispants. Data were normalized to the average CNS area of cas9 control group. F. CRISPR efficacy calculated via TIDE method of individual irf2bpl crispant used in phenotypic study (n = 26 fish). G. Representative local field potential (LFP) recording from cas9 injected control shows baseline activity. H. Representative LFP recording from irf2bpl crispants shows epileptiform events, and a magnified view of the orange box is shown. I. Occurrence of electrographic epileptiform events in cas9 injected control (n = 30 fish) and irf2bpl crispants (n = 24 fish; Chi-square test). Grey, number of fish showed baseline activity; Orange, number of fish showed epileptiform activity. Scale bars as indicated in the figure. Error bars indicate standard deviation (SD). Statistical significance is indicated as *p < 0.05, **p < 0.01, ***p < 0.001