Lei H H, Liu L L, Wang X L, Tie X C, Tian N, Ji Y, Yang Ying
Department of Rehabilitation, Xi'an Children's Hospital, Xi'an 710002, China.
Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital, Xi'an 710002, China.
Zhonghua Er Ke Za Zhi. 2022 Sep 2;60(9):935-939. doi: 10.3760/cma.j.cn112140-20220321-00226.
To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. 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. 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. 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.
探讨2例由MTOR基因变异引起的Smith-Kingsmore综合征患儿的临床表现及遗传学特征，并进行文献复习。回顾性总结2018年4月至2021年4月在西安市儿童医院确诊的2例携带MTOR基因变异患儿的临床资料。以“MTOR”和“Smith-Kingsmore综合征”为关键词，检索截至2021年8月的中国知网、万方数据知识服务平台、PubMed及OMIM。总结MTOR基因变异特点及Smith-Kingsmore综合征患儿的临床表型。2例均为女性，年龄分别为1.5岁和2岁，发病年龄均在婴儿期。均有发育迟缓、巨头畸形及面容异常。全外显子测序均显示MTOR基因存在新发杂合错义变异。1例携带c.5395G>A（p.Glu1799Lys），另1例携带c.7234G>C（p.Asp2412His）。国内尚无MTOR基因变异的文献报道。目前，全球共报道45例伴有详细临床资料的病例。涉及MTOR基因的11种变异，均为杂合错义突变。其中，p.Glu1799Lys为最常见位点（28例，62%）。另1例携带c.7234G>C（p.Asp2412His）的病例此前未见报道。总结这47例（包括这2例）病例，46例有发育迟缓或智力障碍，9例有发育倒退，42例有巨头畸形，30例有面部畸形，16例有肌张力低下，17例有自闭症谱系障碍，3例有多动症，3例有强迫症，13例有眼部疾病，11例有皮肤血管畸形，9例有低血糖。Smith-Kingsmore综合征的主要临床特征包括巨头畸形、发育迟缓或智力障碍、面部畸形，可合并癫痫、自闭症谱系障碍、肌张力低下、低血糖等。MTOR基因变异是Smith-Kingsmore综合征的病因。
