SYNGAP1‐related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights

• Published in: American journal of medical genetics. Part A 2024-08, Vol.194 (8), p.e63606-n/a
• Main Authors: Kim, Hye Jin, Kim, Minhye, Jang, Seoyun, Cho, Jae So, Kim, Soo Yeon, Cho, Anna, Kim, Hunmin, Lim, Byung Chan, Chae, Jong‐Hee, Choi, Jieun, Kim, Ki Joong, Kim, WooJoong
• Format: Article
• Language: English
• Subjects: Age; autism spectrum disorder; Child, Preschool; Developmental Disabilities - genetics; Developmental Disabilities - pathology; Developmental Disabilities - physiopathology; EEG; Electroencephalography; Encephalopathy; Epilepsy; Epilepsy - genetics; Epilepsy - pathology; Epilepsy - physiopathology; Exome Sequencing; Female; Firing pattern; Genetic Association Studies; Genotype; Humans; intellectual disability; Longitudinal Studies; Male; Mutation; Mutation - genetics; neurodevelopmental disorders; Patients; Pediatrics; Phenotype; ras GTPase-Activating Proteins - genetics; Retrospective Studies; synaptic plasticity; Whole genome sequencing
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63606

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole‐exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2–3‐word sentences, corresponding to a developmental age of 2–3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1‐related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.