Case Report
A de novo heterozygous rare variant in SV2A causes epilepsy and levetiracetam-induced drug-resistant status epilepticus

https://doi.org/10.1016/j.ebr.2020.100425Get rights and content
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Highlights

  • SV2A variants are linked to epilepsy in animal studies and rare human reports.

  • Animal studies of SV2A loss of function support decreased efficacy of levetiracetam (LEV).

  • We describe a child with epilepsy and LEV-induced seizure worsening due to a de novo SV2A variant.

  • In patients with rare SV2A variants, LEV should not be used as an antiseizure medication.

  • More studies are needed to establish the spectrum of SV2A-related epilepsy and treatment regimen.

Abstract

SV2A encodes a neuronal synaptic vesicle glycoprotein essential for neurotransmitter release. Altered SV2A function leads to epilepsy in animal models, yet only two reports of human variants have linked SV2A to syndromic drug-resistant epileptic encephalopathies and epilepsy. SV2A is also the binding site for the commonly used antiseizure medication levetiracetam (LEV). However, information about how rare SV2A variants influence LEV response is lacking. Here, we report a two-year-old child with new-onset epilepsy found to have a de novo heterozygous rare variant in SV2A (NM_014849.5:c.1978G>A;p.Gly660Arg) who developed refractory status epilepticus after escalation of LEV treatment for initial baseline seizure control. This report provides additional evidence that monoallelic pathogenic SV2A variants cause epilepsy and that genetic variation in SV2A could lead to paradoxical seizure worsening when treated with LEV.

Keywords

SV2A
Levetiracetam
Epilepsy
Status epilepticus
Genetic

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