Mutations in Munc18‐1/STXBP1 (syntaxin‐binding protein 1) are linked to various severe early epileptic encephalopathies and neurodevelopmental disorders. Heterozygous mutations in the STXBP1 gene include missense, nonsense, frameshift, and splice site mutations, as well as intragenic deletions and duplications and whole‐gene deletions. No genotype–phenotype correlation has been identified so far, and patients are treated by anti‐epileptic drugs because of the lack of a specific disease‐modifying therapy. The molecular disease mechanisms underlying STXBP1‐linked disorders are yet to be fully understood, but both haploinsufficiency and dominant‐negative mechanisms have been proposed. This review focuses on the current understanding of the phenotypic spectrum of STXBP1‐linked disorders, as well as discusses disease mechanisms in the context of the numerous pathways in which STXBP1 functions in the brain. We additionally evaluate the available animal models to study these disorders and highlight potential therapeutic approaches for treating these devastating diseases.

中文翻译：

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STXBP1脑病：临床范围，疾病机制和治疗策略

Munc18-1 / STXBP1（突触素结合蛋白1）中的突变与各种严重的早期癫痫性脑病和神经发育障碍有关。STXBP1基因中的杂合突变包括错义，无义，移码和剪接位点突变，以及基因内的缺失和重复以及全基因缺失。到目前为止，尚未发现基因型与表型的相关性，并且由于缺乏特定的疾病缓解疗法，因此使用抗癫痫药治疗了患者。STXBP1相关疾病的分子疾病机制尚未完全了解，但已提出了单倍机能不全和显性负性机制。这篇综述着重于对STXBP1相关疾病的表型谱的最新了解，以及在STXBP1在大脑中起作用的众多途径的背景下讨论了疾病机制。我们还评估了可用的动物模型来研究这些疾病，并重点介绍了治疗这些破坏性疾病的潜在治疗方法。