Noonan综合征患儿临床表型与基因变异谱分析  

Clinical phenotype and gene variation profile in children with Noonan syndrome

作　　者：陶东英 成胜权 张静静 张惠琴 牛焕红 TAO Dongying;CHENG Shengquan;ZHANG Jingjing;ZHANG Huiqin;NIU Huanhong(Department of Pediatrics,The First Affiliated Hospital of Air Force Military Medical University,Xi'an,Shaanxi 710032,China)

机构地区：[1]空军军医大学第一附属医院儿科,陕西西安710032

出　　处：《中国儿童保健杂志》2023年第12期1365-1369,共5页Chinese Journal of Child Health Care

摘　　要：目的探讨努南综合征(NS)患儿的临床表型与基因学特征,为疾病的早期诊治提供理论依据。方法回顾分析2016年1月—2023年1月诊断的21例NS患儿的临床资料及基因检测结果,并对伴有矮小的患儿身高进行随访。结果21例NS患儿中,男性13例,女性8例,平均确诊年龄为4.6岁(5d~14岁)。21例患儿中,其中12例有特殊面容,11例患有先天性心脏病,9例伴矮身材,6例有喂养困难,3例伴骨骼系统发育异常,3例伴听力障碍,3例伴毛发稀疏,除经典表型外,部分患儿存在牙齿稀疏、脊柱侧弯、畏光、毛囊角化、癫痫、心律失常等少见表型。基因检测结果共发现7种变异基因,其中PTPN117例,BRAF 4例,LZTR13例,SOS13例,KRAS 2例,RAF11例,SHOC21例。其中发现1例合并频发房性心律失常患儿的基因为RAF1,3例伴毛发稀疏患儿中2例基因为RAF1、1例为SHOC2。3例携带LZTR1杂合变异患儿的临床表型仅表现为特殊面容、矮小。9例矮身材患儿给予rhGH治疗,平均治疗时间16.6月,平均身高由-3.62s提升到-3.21s。结论全外显子组测序有助于NS患者的早期诊断;除了NS的经典表型外,频发房性心律失常可能是RAF1突变型NS的一个新的表型谱,毛发稀疏可能是RAF1和SHOC2变异型NS的一个表型谱,LZTR1杂合变异患儿的表型轻微。NS患者短期内rhGH治疗效果尚可,尚未发现rhGH疗效与基因型的明确相关性。Objective To analyze the clinical phenotype and genetic characteristics of children with Noonan syndrome(NS),in order to provide theoretical evidence for early diagnosis and treatment of the disease.Methods A retrospective analysis of the clinical data and genetic testing results of 21 NS children diagnosed from January 2016 to January 2023 were performed.Therapeutic follow-up results of some of the shorter children were also included.Therapeutic follow-up results of some of the shorter children were also included.Results Among the 21 NS patients,there were 13 males and 8 females,with a diagnosis age ranging from 5 days to 14 years old and a mean age of 4.6 years old.Most common clinical features included special facial features(n=12),congenital heart disease(n=11),short stature(n=9),feeding difficulties(n=6),abnormal skeletal development(n=3),hearing disorder(n=3),and sparse hair(n=3).In addition to classic phenotypes,rare phenotypes such as sparse teeth,scoliosis,photophobia,hair follicle keratosis,epilepsy,and arrhythmias were also observed.Seven mutant genes were identified by genetic testing,including PTPN11(n=7),BRAF(n=4),LZTR1(n=3),SOS1(n=3),KRAS(n=2),RAF1(n=1),and SHOC2(n=1).Nine short stature children were treated with rhGH for an average of 16.6 months,with a mean height change from-3.62s to-3.21s.Conclusions Complete exome sequencing is helpful for early diagnosis of NS patients.In addition to the classic phenotype of NS,the RAF1 gene may be associated with frequent atrial arrhythmias,suggesting a new phenotype spectrum.Heterozygous variants in the LZTR1 gene may result in a mild phenotype with sparse hair,which is a rare phenotype of RAF1 and SHOC2 variants of NS.The short-term efficacy of rhGH treatment in NS patients is acceptable,but the correlation between rhGH efficacy and genotype was not clear.

关 键 词：NOONAN综合征 基因 表型 生长激素 

分 类 号：R725.9[医药卫生—儿科]