Abstracts

Rationale: Syngap1 is a rare childhood developmental epileptic encephalopathy (DEE) with defect of the Syngap1 gene on chromosome 6p21.32 location involved with NMDA receptor mediating synaptic plasticity, inserting AMPA receptors in neuronal membranes, as well as dendritic and axon formation.  This autosomal dominant epileptic encephalopathy is associated with autistic and intellectual disabilities as part of their DEE. We present a collection of serial EEG data on initial 30 patients from an international database provided by the Syngap 1 Foundation of patients with Syngap 1 variants showing typical EEG findings and medication treatments for epileptic clinical conditions.

Methods: A total of 30 patients deidentified from database and having serial EEG reports from multiple international medical facilities (United States and Great Britain) and available medical information was reviewed. Patient ages were from age 18 months to 18 years. Northstar IRB reviewed review, Hippa compliance for data collection, and prior consent obtained from patient families by the Syngap1 Foundation to study this deidentified data. Patients had 1 to 13 EEG studies each. Most had 3 or more EEG studies. Medications used were reviewed and any EEG effect noted on review as could best be assessed. Limitations were only interpretive reports were available to review, not actual EEG recordings, and clinical treatment information limited to historical medical reports provided or information in EEG reports.

Results: EEG data start early in life with posterior predominant synchronous and asynchronous spike wave activity with younger children showing more atypical and more continuous slow 2 to 3 Hz spike wave activity between 2 and 7 years of age. Multifocal and generalized spike wave discharges are seen in all reports with limited evidence of medications affecting EEG patterns through toddler age to adolescence in this database. Genetic variance of Syngap 1 did not seem to differentiate common EEG findings. Males were 43% and females were 67%, with EEG patterns similar between sexes. Most common anti-seizure medications ( ASM) were lamotrigine, valproic acid, ethosuximide, levetiracetam, cannabidiol, and clobazam in decreasing order. The effect of ASM on EEG and seizure control could not be determined from the database.

Conclusions: These findings suggest early life EEG patterns that do not normalize over time. EEG patterns involve diffuse cortical regions with generalized epileptic patterns on serial EEG studies with little variation of type of Syngap1 mutation. ASM have no clear effect on EEG patterns over time. Further research in how Syngap1 defect can generate these EEG patterns and how to best manage them is warranted.

Funding: None