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目的:探讨无脑回-巨脑回畸形患儿的临床特征及遗传病因学机制，分析其临床表型与基因型的关系。方法:收集2016年10月至2017年12月在深圳市儿童医院神经内科诊治的21例无脑回-巨脑回畸形患儿的临床资料并进行随访，对所有患儿进行全基因组测序分析。结果:21例患儿中伴癫痫18例(86%)，不伴癫痫3例(14%)；癫痫起病年龄较小，1岁以内起病16例(89%)；其中单纯巨脑回畸形16例(76%)，无脑回合并巨脑回畸形3例(14%)，单纯无脑回畸形2例(10%)。癫痫综合征主要包括West综合征12例(67%)，大田原综合征2例(11%)，其他癫痫性脑病2例(11%)，局灶性癫痫2例(11%)。头颅磁共振成像(MRI)提示单纯巨脑回畸形占多数，其中广泛性巨脑回畸形更多见(56%，9/16例)。全基因组测序结果：检出与无脑回-巨脑回畸形明确相关的致病/疑似致病性单核苷酸变异(SNV)/拷贝数变异(CNV)13例，检出率为62%，n PAFAH1B1基因变异4例，染色体17p13.3微缺失综合征(导致n PAFAH1B1整个基因缺失)6例，n DCX、KIF2A、PIK3R2基因变异各1例。其中n PAFAH1B1基因变异或缺失导致无脑回-巨脑回畸形占比48%(10/21例)，并以顶枕叶或广泛性脑回畸形为主要改变。既往未见报道的新变异有n PAFAH1B1：c.1067G>A、n PAFAH1B1：c.897delT及n KIF2A：c.2225delG。n 结论:无脑回-巨脑回畸形多伴癫痫，以West综合征常见，头颅MRI提示广泛性巨脑回畸形多见。n PAFAH1B1基因变异或缺失是导致无脑回-巨脑回畸形的主要原因。新变异的发现丰富了无脑回-巨脑回畸形的基因型谱数据库。n “,”Objective:To study the clinical features and molecular genetic mechanisms of children with lissencephaly (LIS), as well as to analyze the relationship between genotypes and phenotypes of the disease.Methods:From October 2016 to December 2017, the clinical data and follow-ups of 21 LIS children were collected in the Department of Neurology, Shenzhen Children′s Hospital.Whole genome sequencing (WGS) was performed for genetic testing.Results:Among these 21 cases, 18 cases developed epilepsy (86%), and 3 cases were seizure free (14%). The onset age of children with epilepsy was relatively young, and 16 cases occurred within 1 year old (89%). Among these cases, 16 were pachygyria (76%), 3 cases were agyria combined with pachygyria (14%) and 2 cases were agyria (10%). Epileptic syndromes included 12 cases of West syndrome (67%), 2 cases of Ohtahara syndrome (11%), 2 cases of other epileptic encephalopathy (11%), and 2 cases of focal epilepsy (11%). Brain magnetic resonance imaging(MRI) demonstrated that most cases were pachygyria, among which diffuse pachygyria was more common (56%, 9/16 cases). The results of WGS: 13 pathogenic or likely pathogenic single nucleotide variants (SNV) and copy number variants (CNV) were detected.The total detection rate was 62%, of which 2 cases were frameshift, 1 case was nonsense and 1 case was missense variants of n PAFAH1B1, 6 cases were chromosome 17p13.3 deletion syndrome, thus lea-ding to the whole gene deletion of n PAFAH1B1, and 1 case was missense variant of n DCX, frameshift variant of n KIF2A, and missense variant of n PIK3R2, respectively.Totally, 48% (10/21 cases) of the cases were variants or deletions of n PAFAH1B1, which resulted in lissencephaly in the parietal-occipital region of the brain.Novel variants were n PAFAH1B1: c.1067G>A,n PAFAH1B1: c.897delT and n KIF2A: c.2225delG.n Conclusions:Most cases of LIS accompanied with epilepsy, in which West syndrome was relatively more common.Brain MRI showed that most cases were diffuse pachygyria.The variants and deletions of n PAFAH1B1 was the main genetic cause of LIS.The identification of the novel variants expanded the genotypical spectrum of LIS.n