两例新发SATB2基因突变致语言障碍的临床表型特征并文献复习

Clinical Phenotypic Characteristics of two Cases Caused by Language Disorder with Novel SATB2 Gene Variants and Literature Review

目的探讨SATB2基因突变导致语言障碍的临床特征和诊治方法。方法分析2019~2020年确诊的2例SATB2相关综合征(SATB2-associated syndrome,SAS)患者的临床资料,总结其语言障碍的临床表型特点和诊疗进展,并复习文献。结果两例患儿均为男性,临床表现主要为全面发育迟缓、牙列不齐和口语表达障碍,其中患儿2伴有先天性腭裂。基因检测结果显示,患儿1检测到SATB2基因新生杂合移码突变(c.1259dupA,p.N420Kfs*17);患儿2检测到SATB2基因新生杂合错义突变(c.169G>A,p.G57S)。两个基因突变位点均为既往未曾报道过的新变异位点。结合患儿临床表现及分子遗传检测结果,2例患儿均诊断为SAS。回顾性分析国内外文献报道,86例SAS患者(包括本文报道的2例)均表现为接受性语言障碍和表达性语言障碍,91.7%的患者有牙列发育异常,36.0%的患者有腭裂。SAS患者大多是非语言交流者(66.3%),具有口语交流能力的个体65.4%表现出言语失用的特征。94.9%的SAS患者使用手势替代沟通,并且伴有喂养问题(73.2%)、进食吞咽困难(72.9%)和流涎(60.0%)等口腔功能障碍。结论SATB2基因突变导致不同程度的语言障碍,常伴有口腔发育异常,以言语受限和语言障碍为主的全面发育迟缓是SAS的早期识别症状。临床上需要根据SAS患者口腔功能和语言-言语障碍表型特征制定整体的临床干预和语言康复措施。

Objective To investigate the clinical features,diagnosis,treatment and follow-up of language disorder caused by SATB2 gene mutation.Methods Two children diagnosed with SATB2 associated syndrome(SAS)in the developmental behavior clinic of our center from 2019 to 2020 were retrospectively analyzed.The clinical phenotypic characteristics and treatment of SAS related language disorders in this study and the literatures were reviewed and summarized.Results Both male patients presented main clinical manifestations of general developmental delay,dentition irregularity and expressive language disorder.The second case was also diagnosed with congenital cleft palate.The WES test showed that one de novo heterozygous frameshift variant in SATB2 gene was detected in case 1(c.1259dupA,p.N420Kfs*17);and another de novo heterozygous missense variant in SATB2 gene was detected in case 2(c.169G>A,p.G57S).These two variants had not been reported before.According to the clinical manifestations and genetic test results,the two children were diagnosed as SAS.This study also reviewed 86 SAS patients(including 2 cases reported in this paper)with detailed language features,treatment and follow-up data reported locally and internationally.All patients presented receptive and expressive language disorders,91.7%of them reported abnormal dentition development,and 36.0%reported cleft palate.Most of the people with SAS were nonverbal communicators(66.3%),and 65.4%showed the characteristics of speech apraxia.Moreoer 94.9%of SAS patients used gestures instead of verbal communication and had feeding problems(73.2%),dysphagia(72.9%),and salivation(60.0%).Conclusion SATB2 gene mutation leads to various degree of language disorders,accompanied by oral dysplasia.The early recognition symptoms of SAS are general developmental delay with speech restriction and language disorders.In clinical practice,it is necessary to formulate the overall clinical intervention and rehabilitation plan according to the phenotypic characteristics of oral development and language-speech disorders in SAS patients.