CASE REPORT article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Volume 13 - 2025 | doi: 10.3389/fped.2025.1671464
De Novo Frameshift Mutation in SYNGAP1 Resulting in Autosomal dominant mental retardation type 5 and Autism Spectrum Disorder: A Case Report
Provisionally accepted
- 1School of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
- 2Diagnosis and Treatment Center for Children, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
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Background: Autosomal Dominant Intellectual Disability Type 5 (MRD5) is caused by heterozygous mutations in the SYNGAP1 gene. This gene, located on chromosome 6q21, encodes a synaptic Ras/Rap GTPase-activating protein that regulates Ras/Rap signaling and AMPA receptor trafficking, impacting synaptic plasticity and neuronal homeostasis. According to studies by Chen et al. and Kim et al., the SYNGAP1 gene is localized to dendritic spines of pyramidal neurons in the rodent neocortex. Case Summary: We report a 2-year-10-month-old girl presenting with global developmental delay (GDD) and autistic behaviors, characterized by unsteady gait, inability to stand on one foot, significantly impaired expressive language (maximally three-word phrases), poor response to name, reduced eye contact, and absent joint attention, despite normal hearing. Standardized assessments revealed severe impairments: Gesell Developmental Quotient (DQ) = 36, Childhood Autism Rating Scale (CARS) score = 42 (indicating severe autism), and Autism Diagnostic Observation Schedule (ADOS-2) Module 1 score = 16. Whole-exome sequencing identified a de novo heterozygous frameshift mutation in the SYNGAP1 c.1230delC p. (Ser410ArgfsTer30), classified as pathogenic per ACMG guidelines. Electroencephalography (EEG) revealed no abnormalities, and brain magnetic resonance imaging (MRI) showed no structural lesions. The patient was diagnosed with MRD5 and Autism Spectrum Disorder (ASD). Conclusion: We present a case of SYNGAP1-related MRD5 characterized by significant global developmental delay and autism spectrum disorder, featuring a novel c.1230delC frameshift variant that has not been reported before. This discovery expands clinicians' knowledge of the mutation spectrum and phenotypic variability linked to SYNGAP1, enhancing understanding of genotype-phenotype relationships in SYNGAP1-related conditions.
Keywords: Autism Spectrum Disorder, Global developmental delay, Autosomal dominantmental retardation type 5, Syngap1, Epilepsy
Received: 23 Jul 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 lin, Qi, Xie, Wang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shungzhu lin, 61858@163.com
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