Abstract：
OBJECTIVE: To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation.
METHODS: Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children\'s Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized.
RESULTS: Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5.
CONCLUSIONS: The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.
METHODS: Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children\'s Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized.
RESULTS: Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5.
CONCLUSIONS: The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.
摘要：
目的：探讨SYNGAP1变异的幼儿早期神经发育特征及其基因型-表型相关性。
方法：选择2019年1月至2022年7月转诊至首都儿科研究所附属儿童医院的神经发育障碍（NDDs）幼儿（<5岁）作为研究对象。所有的孩子都接受了全外显子组测序,综合儿科神经心理学评估，家庭隔离分析，和致病性分类。同时,从文献中检索到具有致病性/可能致病性SYNGAP1变异的年轻中国NDD儿童（<5岁），包括详细的临床和基因检测，儿童神经心理和行为量表-修订版2016（CNBS-R2016）的神经发育商（DQ）。还包括没有详细DQ但由医学专业人员评估其发育状况的儿童。神经发育严重程度之间的相关性，总结了合并症和SYNGAP1变体。
结果：招募了4名携带SYNGAP1变异的NDD儿童（1名男性和3名女性，平均年龄34.0±18.2个月)，其中有一个新的变体(c.437C>G，p.S146*).结合从文献中检索到的19例类似病例，23名中国NDD幼儿被纳入我们的研究(8名男性和10名女性，5未知性别，平均年龄37.1±14.2个月)。在19名（82.6％）儿童中发现了功能丧失（LOF）变体。所有儿童在两岁之前都出现了全球发育迟缓（GDD）。此外,16人（69.6%）在27.0±12.1个月时有癫痫发作/癫痫，其中15人与全球发育迟缓无关。肌阵挛性和不存在是癫痫的常见类型。与外显子8至15变异的儿童相比，外显子1至5变异的儿童发育迟缓的严重程度更轻。
结论：SYNGAP1变异体对幼儿（<5岁）的早期神经发育特征包括整体发育迟缓和癫痫发作/癫痫。所有的孩子都可以在两岁前出现GDD。发育迟缓的严重程度可能与SYNGAP1变体的类型和位置有关。
方法：选择2019年1月至2022年7月转诊至首都儿科研究所附属儿童医院的神经发育障碍（NDDs）幼儿（<5岁）作为研究对象。所有的孩子都接受了全外显子组测序,综合儿科神经心理学评估，家庭隔离分析，和致病性分类。同时,从文献中检索到具有致病性/可能致病性SYNGAP1变异的年轻中国NDD儿童（<5岁），包括详细的临床和基因检测，儿童神经心理和行为量表-修订版2016（CNBS-R2016）的神经发育商（DQ）。还包括没有详细DQ但由医学专业人员评估其发育状况的儿童。神经发育严重程度之间的相关性，总结了合并症和SYNGAP1变体。
结果：招募了4名携带SYNGAP1变异的NDD儿童（1名男性和3名女性，平均年龄34.0±18.2个月)，其中有一个新的变体(c.437C>G，p.S146*).结合从文献中检索到的19例类似病例，23名中国NDD幼儿被纳入我们的研究(8名男性和10名女性，5未知性别，平均年龄37.1±14.2个月)。在19名（82.6％）儿童中发现了功能丧失（LOF）变体。所有儿童在两岁之前都出现了全球发育迟缓（GDD）。此外,16人（69.6%）在27.0±12.1个月时有癫痫发作/癫痫，其中15人与全球发育迟缓无关。肌阵挛性和不存在是癫痫的常见类型。与外显子8至15变异的儿童相比，外显子1至5变异的儿童发育迟缓的严重程度更轻。
结论：SYNGAP1变异体对幼儿（<5岁）的早期神经发育特征包括整体发育迟缓和癫痫发作/癫痫。所有的孩子都可以在两岁前出现GDD。发育迟缓的严重程度可能与SYNGAP1变体的类型和位置有关。
