SYNGAP1 유전자 변이와 관련된 뇌전증 및 지적 장애의 스펙트럼
Spectrum of SYNGAP1 gene mutation-related epilepsy and intellectual disability
Abstract
Purpose: Mutations in the SYNGAP1 gene, which encodes the synaptic RAS-GTPase-activating protein 1, which is a protein of the post-synaptic density of glutamatergic neurons, have been reported with intellectual disability, epileptic encephalopathy or autism spectrum disorders. Our objective was to characterize the phenotype spectrum associated with SYNGAP1 mutations. Methods: We identified three patients who had de novo mutations of the SYNGAP1 gene with a customized next generation sequencing (NGS) epilepsy panel, including additionally comparison of the genetic variants in the genes of the child with those in the parents, so called trio analysis. Medical history, neuropsychiatry tests, MRI, and EEG findings were reviewed. Results: Of three patients, two had nonsense mutations and one had missense mutation. Of three, two were confirmed by trio analysis, the other nonsense mutation was not previously reported at normal population and was confirmed, although trio analysis was not performed. All of them have epileptic encephalopathy, including Lennox-Gastaut syndrome and Doose syndtrome, and intellectual disability of varying degrees. It was proved that two of three patients had autism and autistic spectrum disorder. Median age of seizure onset was 28.7 month old (min.=24 month, max.=36 month). All of three patients had myoclonic seizures, including myoclonus which were described as head drops seizures by parents. One of them had absence seizures. Their interictal EEG showed generalized and multifocal epileptiform discharges. Brain MRI scans were all normal. All patients were under treatment with two or three antiepileptic drugs and their seizures were relatively well controlled. Conclusion: SYNGAP1 gene mutation can be identified in a subset of patients with epileptic encephalopathy, intellectual disability, and autism spectrum disorders.