SATB2相关综合征13例病例系列报告

13 children with SATB2-associated syndrome: A case series report

目的总结SATB2相关综合征(SAS)的临床及遗传学特征,为早期干预及产前咨询提供依据。方法回顾性分析2016年1月至2020年6月于复旦大学附属儿科医院就诊且基因诊断为SAS患儿的临床资料和基因检测结果。结合人类基因突变数据库(HGMD)和PubMed,对SAS的临床表型及遗传特征进行文献复习。结果13例SAS患儿进入本文分析,男7例,女6例,样本检测年龄为生后3 d至9岁7月(M为14月龄)。13例均存在发育迟缓,>1岁的患儿均出现语言发育障碍。8例行头颅MR检查,7例提示脑成像异常。4例癫癎发作。2例骨发育不良,4例四肢肌张力低下,2例心血管畸形。13例均有小颌和牙齿畸形,4例腭裂,3例体重低于同龄儿2 SD,2例流涎,1例角膜白斑。4例并发肺部反复感染,1例合并先天性喉软化及声带麻痹。13例患儿检测到13种SATB2基因杂合变异,包括6种错义变异(E436A、L261P、L626P、R399C、A590T、E566K),2种无义变异(Q666Ter、R239 Ter),5种染色体2q32-2q37区缺失/重复导致的拷贝数变异,其中R239 Ter和E566K为HGMD已收录的致病位点,其余11种均为新变异。结论SAS可累及多系统,需通过基因检测协助明确诊断。建议将SATB2基因作为原因不明的神经发育障碍性疾病的重要候选基因进行筛查和诊断。

Objective To summarize the clinical and genetic characteristics of SATB2-associated syndrome (SAS), and to provide evidence for early intervention and prenatal counseling. Methods Children diagnosed as SAS by genetic testing were recruited from January 2016 to June 2020 in Children's Hospital of Fudan University. We analyzed the clinical and genetic features of these patients retrospectively. According to Human Gene Mutation Database(HGMD) and PubMed, literature on clinical phenotype and genetic characteristics of SAS were reviewed. Results Thirteen children with SAS were included in this study, consisting of 7 males and 6 females. The age of genetic test ranged from 3 days to 9 years and 7 months (median age of 14 months). After psychomotor development was evaluated in 13 patients during the follow-up, all of them presented with developmental delay and all children over 1 year old had language retardation. Of the 8 cases undergoing brain MR examinations, 7 cases showed abnormal brain imaging. Four cases presented epilepsy. Two patients presented bone dysplasia and 4 individuals were hypotonia. Congenital heart defects were identified in 2 children. Physical examination showed that all of 13 children had malformation of small jaw and teeth, 4 cases were diagnosed with cleft palate, 3 patients' weight was 2 standard deviations lower than those of their peers, 2 children presented salivation, and 1 case occurred corneal leukoplakia. There were 4 cases of recurrent pulmonary infection and 1 patient accompanied with congenital laryngomalacia and vocal cord paralysis. Thirteen mutations of SATB2 were detected in 13 patients, including 6 missenses mutations (p.E436A, p.L261P, p.L626P, p.R399C, p.A590T, p.E566K ), 2 nonsense mutation (Q666Ter, R239 Ter), and 5 copy number variations resulting from deletion/duplication in region 3 of the long arm of chromosome 2. The mutations of R239 Ter and E566K were recorded in HGMD, and other variations were novel. Conclusion SATB2-associated syndrome involves multiple system abnormalities, which needs to be confirmed by genetic testing. SATB2 gene can be regarded as an important candidate gene for the screening and diagnosis of neurodevelopmental disorders with unknown causes.