SYNGAP1基因变异相关常染色体显性智力障碍5型8例并文献复习

Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations:a report of 8 cases and literature review

目的 总结SYNGAP1基因相关常染色体显性智力障碍5型患儿临床表型及遗传学特点。方法 回顾性分析中南大学湘雅医院儿科诊治的8例SYNGAP1基因相关智力障碍患儿的临床资料。结果 8例患儿的平均起病年龄为9月龄,均伴有中重度发育迟缓(语言落后为著),其中7例患儿伴癫痫发作。8例患儿中7例为新发杂合变异(3例移码变异、2例无义变异和2例错义变异),1例为6p21.3微缺失。目前已报道的中国SYNGAP1基因变异相关智力障碍患儿(包括该研究)有48例,其中40例伴癫痫发作,癫痫发作平均起病年龄为31.4月龄,多为移码变异(15/48,31%)和无义变异(19/48,40%)。治疗上,有癫痫用药史记录的33例患儿中,丙戊酸抗癫痫发作治疗对多数患儿有效(85%,28/33),其中48%(16/33)患儿丙戊酸单药或联合用药治疗达到发作完全控制。结论 SYNGAP1基因相关常染色体显性智力障碍5型患儿起病年龄早,多数患儿伴癫痫发作,以移码变异和无义变异为主,丙戊酸抗癫痫发作治疗对多数患儿有效。

Objective 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.