Abstracts

Rationale: Background Early infantile epileptic encephalopathy (EIEE) was classically characterized as “lesional epilepsy”. It is now known that EIEE can be genetic. STXBP1, which encodes syntaxin binding protein 1, is a gene that has recently been found to cause EIEE. The phenotype of EIEE caused by STXBP1 mutations is described in the literature as most consistent with severe developmental delay with intractable epilepsy. As more cases have been reported, the clinical phenotype is becoming more heterogeneous. Objectives We have sought out to broaden the clinical phenotype in patients with early epileptic encephalopathy associated with STXBP1 mutations, particularly focusing on seizure semiology, seizure control, and developmental outcomes.Methods: Patients and Methods We analyzed magnetic resonance imaging (MRI) of the brain, electroencephalography (EEG), clinical, and developmental outcomes in a cohort of four children with EIEE secondary to de novo STXBP1 mutations across three medical centersResults: Results Imaging: All four patients have normal brain MRI studies. Neurodiagnostics and semiology: Patient A has significantly abnormal EEGs that have clinically transitioned from Ohtahara Syndrome to Infantile Spasms to Lennox-Gastaut Syndrome. Patients B and C have mild EEG abnormalities clinically consistent with focal epilepsy. Patient D has had hypsarrhythmia on initial EEG however with more recent EEGs suggestive of an encephalopathy with focal slowing. Seizure onset: Patients A and C developed seizures within the first week of life whereas Patient B and D developed seizures between 2-4 months of age. Seizure control: All 4 patients had differing responses to anti-seizure medication and varying difficulty with seizure control. Development: Patient A has significant global developmental delay without language or the ability to sit. Patient B has some language and is ambulatory with mild motor delays. Patient C, does not have any language however is ambulatory with moderate motor delays. Patient D does not demonstrate any developmental delay. Patients are A, B and C are ataxic. Genetics: All 4 patients have de novo mutations of the STXBP1 gene.Conclusions: Conclusions STXBP1 is a newly reported genetic cause of EIEE with less than 50 cases in the literature. In our case series, we demonstrate that the phenotypic spectrum is broad with respect to seizure semiology, level of seizure intractability, characteristic EEG findings, and developmental outcomes. Overall, we are demonstrating cases that suggest that the amount of disability may be more variable with the possibility of a less severe prognosis.