Abstracts

Rationale: Early infantile epileptic encephalopathy (EIEE) and early myoclonic encephalopathy (EME) have been historically depicted as separate entities, with EIEE being associated with structural brain lesions, whereas non-structural/metabolic causes have been implicated in EME. However, these diagnoses have more recently been considered part of a spectrum of disorders, characterized by early-onset epileptic encephalopathy with burst suppression (EOEE-BS). Though there have been some well-described genetic, metabolic, and structural abnormalities identified as causative, with the advent of clinically available genetic epilepsy panels and whole exome sequencing, rare genetic disorders are more frequently being identified in these patients. Methods: We performed a retrospective chart review on consecutive patients at a single tertiary care pediatric hospital who presented with severe early-onset epilepsy and suppression-burst pattern on EEG. Data included continuous video-EEG monitoring, brain magnetic resonance imaging (MRI), serum and CSF biochemical analyses, and genetic testing including whole exome sequencing (WES). Results: Definitive diagnoses were made based on WES in 3 patients with EOEE-BS. Neurodiagnostics and Semiology: Patient A developed tonic stiffening of extremities with autonomic fluctuations at 12 hours of life. Patient B developed myoclonic and hemi-clonic jerks at 2 days of life. Patient C demonstrated myoclonic seizures at 24 hours of life. All three patients' EEG's demonstrated a burst suppression pattern with multifocal epileptiform activity. Imaging: Patient A had a normal brain MRI, whereas patients B and C had structural abnormalities. Patient B had small areas of parenchymal and perivascular hemorrhage attributed to possible septic emboli and birth trauma, whereas Patient C demonstrated structural abnormalities including pontocerebellar hypoplasia and simplified gyral pattern.  Genetics: Whole Exome sequencing in Patient A revealed a novel pathogenic variant in the SCN2A gene (4984A>G, p.N1662D).  Genetic testing in Patient B revealed 2 compound heterozygous pathogenic variants in the ALDH7A1 gene in trans configuration. Patient C was found to have a novel pathogenic variant in the CASK gene. Conclusions: Early-onset epileptic encephalopathies with burst suppression represent a heterogeneous group of patients. Our findings add to the growing list of identified genetic variants implicated in EOEE-BS. Whole exome sequencing in this population may help to diagnose, prognosticate, and potentially guide therapy for patients with EOEE-BS. Goals of early and targeted intervention, including dietary/metabolic therapies, anti-seizure drugs with disease-compatible mechanisms of action, and potential gene-based treatments may allow for improved outcomes. Funding: None