Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation

Dilena, Robertino; Striano, Pasquale; Traverso, Monica; Viri, Maurizio; Cristofori, G.; Tadini, L.; Barbieri, S.; Romeo, Antonino; Zara, Federico

doi:10.1016/j.braindev.2015.07.002

Cited by 49 publications

(46 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, it is hypothesized that the mutation itself and other genetic or environmental factors contribute to the individual phenotype. Dilena et al reported a case manifesting an EE with a de novo heterozygous mutation (c.[922A>T]p.[Lys308(*)]) in the STXBP1 gene who presented a dramatic response to LEV with full epilepsy control and EEG normalization. This led to the adoption of LEV as the potential first choice treatment for epilepsy based on the specific ability of LEV to modulate the synaptic vesicle release affected by STXBP1 mutations.…”

Section: Discussionmentioning

confidence: 99%

De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy

Chen

Wang

et al. 2018

Genes Brain and Behavior

View full text Add to dashboard Cite

To detect syntaxin-binding protein 1 (STXBP1) mutations in Chinese patients with early onset epileptic encephalopathy (EOEE) of unknown etiology. Targeted next-generation sequencing was used to identify STXBP1 mutations in 143 Chinese patients with EOEE of unknown etiology. A filtering process was applied to prioritize rare variants of potential functional significance. Then Sanger sequencing was employed to validate the parental origin of the variants. Detailed clinical and genetic data were collected for 9 STXBP1-positive patients. Eight de novo heterozygous STXBP1 mutations were identified in 9 patients; 5 were novel mutations (c.1155delC, c.1030-1G>A, c.217G>C, c.268G>C, c.1480_1481 insT) and 3 were previously reported (c.1216C> T, c.1217G>A [2 cases], c.875G>A). Two patients had Ohtahara syndrome and 1 had West syndrome at onset, whereas the other 6 presented with EOEE that did not fit a specific recognized epilepsy syndrome. Six of these patients later evolved to West syndrome. All but 2 cases were prescribed more than 2 antiepileptic drugs (AEDs) plus other regimens. Four subjects showed good responses to levetiracetam (LEV) alone or in combination with other AEDs, and one case (1/3) achieved complete freedom from seizures with a ketogenic diet (KD). All patients exhibited severe to profound global developmental delay. Five novel heterozygous de novo STXBP1 mutations were discovered in patients with EOEE from China. STXBP1 mutational analysis should be performed in cases of EOEE of unknown etiology. LEV as monotherapy or adjunctive therapy with other regimens, as well as KD should be considered for management of this patient group.

show abstract

Section: Discussionmentioning

confidence: 99%

De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy

Chen

Wang

et al. 2018

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…Several different pathogenic variants causing EIEE with severe intellectual disability and abnormalities of tone and movement have been described. 57 Targeted resequencing of 67 SCN1A-negative DS patients identified three pathogenic STXBP1 variants. STXBP1 epilepsy appears to be characterized by tonic seizures and/or spasms, both of which are unusual in DS.…”

Section: Stxbp1mentioning

confidence: 99%

Dravet syndrome and its mimics: Beyond SCN1A

et al. 2017

View full text Add to dashboard Cite

Although most cases of DS arise from SCN1A variants, numerous other genes cause encephalopathies that are clinically similar. Increasingly, a tendency is noted to define newly described epileptic disorders primarily in genetic terms, with clinical features being linked to genotypes. As genetic diagnosis becomes more readily available, its potential to guide pathophysiologic understanding and therapeutic strategy cannot be ignored. Clinical assessment remains essential; the challenge now is to develop a gene-based taxonomy that complements traditional syndromic classifications, allowing elements of both to inform new approaches to treatment.

show abstract

“…Some of the patients also have mental retardation, ataxia, and dyskinetic movements (Deprez et al, 2010). Treatment with levetiracetam in patients effectively Presynaptic Drug Targets managed seizures that were refractory to other antiepileptic drugs (Vatta et al, 2012;Dilena et al, 2016). This may be due to levetiracetam's unique mechanism of action involving SV2A.…”

Section: Snare-associated Proteinsmentioning

confidence: 99%

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Kavalali

2017

Pharmacol Rev

View full text Add to dashboard Cite

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation

Cited by 49 publications

References 9 publications

De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy

De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy

Dravet syndrome and its mimics: Beyond SCN1A

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Contact Info

Product

Resources

About