Efficacy of levetiracetam in STXBP1 encephalopathy with different phenotypic and genetic spectra

Wang, Qiuhong; Cao, Jia-Jie; Zou, Li‐Ping; Wang, Yangyang; Zhang, Mengna; Liu, Liying; Wang, Jing; Lü, Qian; He, Wen; Shen, Yan-Wen; Chen, Huimin; Luo, Xiaomei; Chen, Qian

doi:10.1016/j.seizure.2021.12.006

Cited by 4 publications

(5 citation statements)

References 37 publications

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“…During development and postnatal life, STXBP1 is expressed ubiquitously throughout the brain and neocortex. Therefore, the variants in STXBP1 gene have been reported to be related to STXBP1 encephalopathies, presenting as developmental and epileptic encephalopathy (O’Brien et al , 2019; Cousin et al , 2021; Wang et al , 2022). These clinical features are all consistent with that of our patient.…”

Section: Discussionmentioning

confidence: 99%

“…Syntaxin binding protein 1 ( STXBP1 ) gene mutation can cause developmental and epileptic encephalopathy 4 (DEE4, also known as encephalopathy), which mainly presents as a developmental and epileptic encephalopathy. DEE4 has a wide phenotypic spectrum and is caused by a neurodevelopmental disorder related to the deficiency of STXBP1, which plays a critical role in the release of neurotransmitters (O’Brien et al , 2019; Cousin et al , 2021; Wang et al , 2022).…”

Section: Introductionmentioning

confidence: 99%

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Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay

Wang,

Cui,

Ling

et al. 2023

Psychiatric Genetics

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Autosomal dominant sleep-related hypermotor epilepsy is a rare disease caused by pathogenic variants of CHRNB2, CHRNA4, and CHRNA2 genes, with nocturnal frontal lobe epilepsy as the main symptoms. Syntaxin binding protein 1 (STXBP1) gene mutation can cause developmental and epileptic encephalopathy 4, mainly presenting as a developmental and epileptic encephalopathy. We performed the exome-targeted next-generation sequencing in our patient and identified two heterozygous variants: c.963 + 2T>C of STXBP1 and c.520_527delinsTGCTAC (p.R174Cfs*16) of CHRNB2. Molecular analysis was performed of the variant c.963 + 2T>C. Aberrantly spliced products were observed, proving the pathogenicity of this variant. Refractory seizures and developmental delay could be explained. Although the variant c.520_527delinsTGCTAC could cause the truncation of the proteins, it was ultimately determined to be nonpathogenic. The startle-like responses that occurred occasionally during the night were ultimately determined to be an uncommon phenotype caused by the STXBP1 variant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay

Wang,

Cui,

Ling

et al. 2023

Psychiatric Genetics

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“…A comparison of 26 patients initiated on LEV compared to 10 patients on other antiseizure medications showed a significantly greater number of patients with >50% seizure reduction at 6 months (88% vs. 50%). Although LEV did lead to a reduction in seizure frequency, there was no observed difference in achieving seizure freedom [60]. A few case reports anecdotally state that levetiracetam has benefits as well [42,61].…”

Section: Treatmentmentioning

confidence: 93%

“…Based on our current understanding of STXBP1-related disorders, several targeted therapies have been developed to help treat this patient population. Levetiracetam (LEV), an antiseizure medication whose mechanism of action targets the synaptic vesicle protein SV2A, has been found to have some benefit in patients with STXBP1 disorders [60]. A comparison of 26 patients initiated on LEV compared to 10 patients on other antiseizure medications showed a significantly greater number of patients with >50% seizure reduction at 6 months (88% vs. 50%).…”

Section: Treatmentmentioning

confidence: 99%

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Freibauer,

Wohlleben,

Boelman

2023

Genes

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In recent years, the affordability and availability of genetic testing have led to its increased use in clinical care. The increased frequency of testing has led to STXBP1 variants being identified as one of the more common variants associated with neurological disorders. In this review, we aim to summarize the common clinical phenotypes associated with STXBP1 pathogenic variants, provide an overview of their known natural history, and discuss current research into the genotype to phenotype correlation. We will also provide an overview of the suspected normal function of the STXBP1-encoded Munc18-1 protein, animal models, and experimental techniques that have been developed to study its function and use this information to try to explain the diverse phenotypes associated with STXBP1-related disorders. Finally, we will explore current therapies for STXBP1 disorders, including an overview of treatment goals for STXBP1-related disorders, a discussion of the current evidence for therapies, and future directions of personalized medications for STXBP1-related disorders.

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“…STXBP1-DEE is associated with asymmetric tonic posturing or sequential seizures (tonic, autonomic, clonic, and epileptic spasms) (Figure 2C). Several studies have documented excellent responses to levetiracetam [7,27,29,[37][38][39][40].…”

Section: Scn2a-deementioning

confidence: 99%

Could Neonatal Electroclinical Syndromes Orchestrate Diagnosis and Treatment?

Andrade Machado

2024

J Exp Neurol

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Introduction: Neonatal seizures are associated with neurodevelopmental impairments. Implementing long-term video-EEG monitoring in the neonatal intensive care unit became the gold standard for seizure diagnosis. During the neonatal period, seizures can be associated with an acute brain insult called acute symptomatic seizures (ASS) or being part of neonatal epilepsy that may have a structural, metabolic, or genetic cause. This distinction impacts patient workup and management. Objectives: To facilitate a guide to differentiate ASS from neonatal epilepsy, and to correlate different electroclinical seizure patterns with a specific etiology. Methods: A narrative review was performed. MEDLINE, Embase, and PubMed were used to gather data for this narrative review. The following keywords were applied to focus on original research and case reports: epileptic encephalopathy, developmental Epileptic encephalopathy and neonatal seizures, neonatal genetic encephalopathies, Otahara syndrome, neonatal channelopathies, and neonatal seizure classification. Conclusions: Strict electroclinical semiology is the backbone for diagnosing neonatal seizures. The EEG and ictal semiology help with the diagnosis and the treatment. The neonatal seizure classification should be expanded to include the EEG pattern. Lumping them in a better classificatory system will prevent unnecessary and hazardous medication.

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Efficacy of levetiracetam in STXBP1 encephalopathy with different phenotypic and genetic spectra

Cited by 4 publications

References 37 publications

Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay

Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Could Neonatal Electroclinical Syndromes Orchestrate Diagnosis and Treatment?

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