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Review
. 2023 Dec 5;14(12):2179.
doi: 10.3390/genes14122179.

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

Alexander Freibauer  1   2 , Mikayla Wohlleben  2 , Cyrus Boelman  1   2
Affiliations
Review

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

Alexander Freibauer et al. Genes (Basel). .

Abstract

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.

Keywords: Munc18-1; SNARE protein; STXBP1; developmental and epileptic encephalopathy; epilepsy; genetics; intellectual disability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Physiological Functions of Munc18-1, the protein encoded by STXBP1. Munc18-1 has numerous physiologic functions. It plays an important role in regulating SNARE complex formation (A), Dense-core vesicle release (B), regulation of F-Actin network (C), anterograde and retrograde transport of vesicles and syntaxin 1A (D), and is involved in neuronal viability (E).
Figure 2
Figure 2
Potential pathophysiological mechanisms of STXBP1-related disorders. Normally, there is a balance of excitatory (Glutamate) and inhibitory (GABA) inputs (A). In STXBP1-related disorders, it is thought that synaptic dysfunction upsets the balance of excitation/inhibition (E/I). The three proposed mechanisms of how there can be a disruption of this balance are either localized GABA associated neuron dysfunction (B), impaired excitatory transmission (C), or a breakdown in synchrony of GABAergic/glutamatergic neurons (D).
See this image and copyright information in PMC

References

    1. Verhage M., Sørensen J.B. SNAREopathies: Diversity in Mechanisms and Symptoms. Neuron. 2020;107:22–37. doi: 10.1016/j.neuron.2020.05.036. - DOI - PubMed
    1. Xian J., Parthasarathy S., Ruggiero S.M., Balagura G., Fitch E., Helbig K., Gan J., Ganesan S., Kaufman M., Ellis C., et al. Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain. 2022;145:1668–1683. doi: 10.1093/brain/awab327. - DOI - PMC - PubMed
    1. Na J.-H., Shin S., Yang D., Kim B., Kim H.D., Kim S., Lee J., Choi J., Lee S., Kang H. Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy. Brain Dev. 2020;42:438–448. doi: 10.1016/j.braindev.2020.02.004. - DOI - PubMed
    1. Liu L.-Y., Lu Q., Wang Q.-H., Wang Y.-Y., Zhang B., Zou L.-P. Diagnostic yield of a multi-strategy genetic testing procedure in a nationwide cohort of 728 patients with infantile spasms in China. Seizure. 2022;103:51–57. doi: 10.1016/j.seizure.2022.10.014. - DOI - PubMed
    1. Nagarajan B., Gowda V.K., Yoganathan S., Sharawat I.K., Srivastava K., Vora N., Badheka R., Danda S., Kalane U., Kaur A., et al. Landscape of genetic infantile epileptic spasms syndrome-A multicenter cohort of 124 children from India. Epilepsia Open. 2023;8:1383–1404. doi: 10.1002/epi4.12811. - DOI - PMC - PubMed

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