(845) Early Myoclonic Encephalopathy with a Novel Pathogenic Variant in the STXBP1 Gene: First case reported in Ecuador

This abstract has been invited to present during the Better Patient Outcomes through Diversity Platform poster session

Rationale: Early Myoclonic Encephalopathy (EME) is a rare and severe form of epilepsy, for which not all genetic causes have been identified. Initial presentation is in the neonatal period or first months of life. In most cases, patients develop myoclonic seizures at onset that may occur up to hundreds of times per day. They later develop early onset epileptic spams and refractory focal seizures. It is usually accompanied by intellectual disability, behavior disorders, hypotonia and movement disorders including ataxia, dystonia, and others. On the electroencephalogram a burst suppression pattern is present usually during sleep. (Neurology 2016; 86:1–9)A limited number of genes have been associated with this disease. For instance an alteration in the Syntaxin-binding protein 1 (STXBP1) is a known etiology. This gene plays a key role in synaptic vesicle docking and fusion, which leads to inhibitory neurotransmitters release. We present the first ever reported case of a STXBP1-related condition in Ecuador.

Methods: Patient is a two-month-old male, with a history of intrauterine growth restriction, who presented with frequent myoclonic seizures. Seizure semiology was characterized by rapid flexion of upper and lower extremities with upper deviation of the gaze. In addition, he presented with dysphagia resulting in micro aspirations and failure to thrive, for which he required a gastrostomy tube. Magnetic resonance images and spectroscopy yielded no evidence of focal structural abnormalities. Electroencephalogram showed a typical burst suppression pattern (Figure 1) and the presence of frequent myoclonic seizures in periods of sleep and wakefulness. Patient showed partial response to treatment with high dose Levetiracetam and Phenobarbital.A comprehensive epilepsy gene panel showed a novel pathogenic variant in STXBP1, Exon 12, c.980dup (p.Ser328Valfs*25), not previously described in literature.

Results: This sequence shift generates a premature translational stop signal that is expected to result in a missing or disrupted protein product.The mentioned variant has not yet been reported in the literature regarding individuals with STXBP1-related conditions, neither in population databases (ExAC no frequency). Loss-of-function variants in STXBP1 are known to be pathogenic. (Epilepsia, 51(12):2397–2405, 2010)

Conclusions: To the best of our knowledge, we present the first reported case of a pathologic variant in the STXBP1 gene producing EME disease in Ecuador.
This case demonstrates the importance of increased access to epilepsy genetic panels in developing countries as they can provide early diagnosis and, in determined cases, improve the probability of receiving an appropriate treatment and care.

Funding: Please list any funding that was received in support of this abstract.: No funding
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