Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review.
10.7499/j.issn.1008-8830.2301054
- Author:
Xiao-Le WANG
1
;
Ya-Nan TIAN
;
Chen CHEN
1
;
Jing PENG
1
Author Information
1. Department of Pediatrics, Xiangya Hospital of Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- Keywords:
Child;
Developmental retardation;
Epilepsy;
Mental retardation;
SYNGAP1 gene
- MeSH:
Child;
Humans;
Intellectual Disability/diagnosis*;
Codon, Nonsense;
Retrospective Studies;
Valproic Acid;
ras GTPase-Activating Proteins/genetics*;
Mutation;
Seizures/genetics*
- From:
Chinese Journal of Contemporary Pediatrics
2023;25(5):489-496
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations.
METHODS:A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University.
RESULTS:The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy.
CONCLUSIONS:Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.
