11例儿童RAS通路病的临床特点和基因突变类型

Clinical Characteristics and Gene Mutation Types of 11 Cases of RASopathies in Childhood

【目的】总结5种亚型儿童RAS通路病的临床特点及基因变异类型,分析Ⅰ型神经纤维腺瘤病(NF1)、努南综合征(NS)、多色素痣型努南综合征(NSML)、科斯特洛综合征(CS)和心-面-皮肤综合征(CFC)的临床共性和特性,提高临床医生对RAS通路病的认识和诊治水平。【方法】回顾性分析我院2015年10月至2018年6月期间确诊的11例RAS通路病患者的临床资料及基因突变类型。【结果】11例RAS通路病患儿的发病年龄为6月～12岁,常见临床表现包括:身材矮小、特殊面容、先天性心脏病、皮肤牛奶咖啡斑、运动发育落后、血小板减少、癫痫、肌张力异常、隐睾等,共检测出5种基因突变类型,包括NF1基因、PTPN11基因、RAF1基因、BRAF基因和HRAS基因。【结论】RAS通路病是丝裂原活化蛋白激酶通路异常引起的一组遗传性生长发育异常综合征。因此,RAS通路病常伴有特殊面容、运动发育落后、心血管、皮肤、骨骼、神经等多系统异常以及肿瘤易感性等共同表现。但因基因突变位点的差异,各类型间亦存在相对特异的表现。另外,因肿瘤易感性是RAS通路病的共性之一,肿瘤监测是随访过程的重要项目。

【Objective】Through summarizing the clinical manifestations and gene mutations of 5 types of RASopathies in childhood including Neurofibromatosis type1(NF1),Noonan syndrome(NS),Noonan syndrome with multiple lentigines(NSML),Costello syndrome(CS)and cardio-facio-cutaneous syndrome(CFC)and analyzing their commonalities and characteristics,to deepen the clinician′s understanding of the RASopathies and improve the domestic doctors′ diagnosis and treatment level of RASopathies.【Methods】The clinical data and gene mutation types of 11 patients of RASopathies who were diagnosed in Sun Yat-Sen Memorial Hospital from January 2015 to May 2018 were retrospectively analyzed.【Results】The age of onset ranged from 6 months to 12 years and the main clinical manifestations of 11 patients included:short stature,craniofacial features,congenital heart defect,café-au-lait macules,developmental delay,thrombocytopenia,seizures and dystonia,cryptorchidism,etc. Five gene mutations were detected including NF1 gene,PTPN11 gene,RAF1 gene,BRAF gene and HRAS gene.【Conclusions】The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway.The RAS/MAPK pathway plays an important role in regulating growth development,promoting cell proliferation,differentiation,metabolism,and signal transduction of various hormones. Therefore,they share many overlapping characteristics,including craniofacial features,growth retardation,cardiac malformations,cutaneous and musculoskeletal abnormalities,neurocognitive impairment and tumor susceptibility. However because of mutations at different points in the pathway. In addition features of RASopathies. Therefore,tumor monitoring is one of the most important contents in the follow-up process.