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Case Reports
. 2024 Mar 21:15:1359287.
doi: 10.3389/fneur.2024.1359287. eCollection 2024.

SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings

Bin Ren #  1 , Xiaoyan Wu #  1 , Yuqiang Zhou #  1 , Lijuan Chen  1 , Jingzi Jiang  2
Affiliations
Case Reports

SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings

Bin Ren et al. Front Neurol. .

Abstract

The SYN1 gene encodes synapsin I, variants within the SYN1 gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with SYN1 variants and explores the genotype-phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties. His elder brother exhibited a distinct clinical phenotype, experiencing sudden seizures during sleep at the age of 16, accompanied by hippocampal sclerosis. Whole exome sequencing (WES) confirmed a pathogenic SYN1 variant, c.1647_1650dup (p. Ser551Argfs*134), inherited in an X-linked manner from their mother. Notably, this variant displayed diverse clinical phenotypes in the two brothers and one previously reported case in the literature. Retrospective examination of SYN1 variants revealed an association between truncating variants and the pathogenicity of REs, and non-truncating variants are more related to developmental delay/intellectual disability (DD/ID). In summary, this study contributes to understanding complex neurodevelopmental disorders associated with SYN1, highlighting the clinical heterogeneity of gene variants and emphasizing the necessity for comprehensive genetic analysis in elucidating the pathogenic mechanisms of such diseases.

Keywords: SYN1; bathing epilepsy; clinical heterogeneity; genotype–phenotype correlation; reflex epilepsy.

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Conflict of interest statement

BR, XW, YZ, and LC were employed by the company Shanghai Nyuen Biotechnology Co., Ltd. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Identification of a frameshift variant in SYN1. Pedigree chart and Sanger confirmation of the family. Individuals with the SYN1 variant are represented with an asterisk (*) symbol.
Figure 2
Figure 2
Schematic representation of the SYN1 gene. Exons 1–13 are depicted, truncating variants depicted above, non-truncating variants depicted below, the variants Thr567Ala, Ala51Gly, and Gly240Arg are removed. The conserved A (N-terminal highly phosphorylated domain), B (linker), and C (functional domain) domains are depicted in yellow, blue, green, respectively; the D, E domains in pink, and purple.
See this image and copyright information in PMC

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The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Project of Guangxi Natural Science Foundation (grant no. 2022GXNSFAA103020).

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