Objective: To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. Methods: The clinical data of 2 children carrying MTOR gene variant, diagnosed at Xi'an Children's Hospital from April 2018 to April 2021, were retrospectively summarized."MTOR"and"Smith-Kingsmore syndrome"were used as key words to search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and OMIM up to August 2021. The characteristics of MTOR gene variation and the clinical phenotype of children with Smith-Kingsmore syndrome were summarized. Results: Two children were both females, aged 1.5 years and 2 years respectively, the onset age were both in infancy. They both had developmental delay, megalencephaly and abnormal face. Both whole exome sequencing revealed a de novo heterozygous missense variant in MTOR gene. One case carried c.5395G>A (p.Glu1799Lys) and the other case carried c.7234G>C (p.Asp2412His). There was no literature of MTOR gene variation in Chinese. So far, a total of 45 cases were reported worldwide with detailed clinical information. Eleven variations in MTOR gene were involved, which were all heterozygous missense mutations. Among them, p.Glu1799Lys was the most common sites (28 cases,62%). Another case carried c.7234G>C (p.Asp2412His) was not reported before. Summarizing the 47 cases (including these 2 cases), 46 cases had developmental delay or intellectual disability, 9 cases had developmental regression,42 cases had megalencephaly, 30 cases had facial malformation,16 cases had hypotonia, 17 cases had autism spectrum disorders, 3 cases had hyperactivity, 3 cases had obsessive compulsive disorder, 13 cases had eye diseases, 11 cases had cutaneous vascular malformation, and 9 cases had hypoglycemia. Conclusions: The main clinical features of Smith-Kingsmore syndrome include megalencephaly, developmental delay or intellectual disability, and facial malformation, which can be combined with epilepsy, autism spectrum disorder, hypotonia, hypoglycemia and so on. The variation of MTOR gene is the cause of Smith-Kingsmore syndrome.
目的： 总结MTOR基因变异致Smith-Kingsmore综合征的临床表型及遗传学特点。 方法： 回顾性分析2018年4月至2021年4月在西安市儿童医院明确诊断的2例MTOR基因变异致Smith-Kingsmore综合征患儿的临床资料。以“MTOR”和“Smith-Kingsmore”为关键词分别在中国期刊全文数据库（CNKI）、万方数据知识服务平台、PubMed、OMIM进行检索（建库至2021年8月），总结MTOR基因变异特点及其导致Smith-Kingsmore综合征患儿的临床特点。 结果： 2例患儿均为女性，分别为1岁6月龄和2岁，发病年龄均在婴儿期，均表现为全面发育迟缓、巨头畸形及面容异常，全外显子基因检测均发现MTOR基因新发杂合变异，1例携带c.5395G>A（p.Glu1799Lys），另1例携带c.7234G>C（p.Asp2412His）。文献检索未见中文文献，国外文献报道具有详细表型的MTOR基因变异致Smith-Kingsmore综合征患者45例，共发现11个基因变异，均为杂合错义变异，28例（62%）患者携带c.5395G>A（p.Glu1799Lys），考虑为热点变异。c.7234G>C（p.Asp2412His）未检索到相关文献。结合本组2例患儿，共总结47例患者临床特点，其中发育迟缓或智力障碍46例，发育倒退9例，巨头畸形42例，面容异常30例，肌张力减低16例，合并孤独症谱系障碍17例、多动症3例、强迫症3例，眼部疾病13例，皮肤血管畸形11例，低血糖9例。 结论： Smith-Kingsmore综合征主要临床表现包括发育迟缓或智力障碍、巨头畸形、面部畸形，可合并癫痫、孤独症谱系障碍、肌张力低下、低血糖等表现。MTOR基因变异是其致病原因。.