努南样综合征伴毛发松动患儿的临床特征分析  

Clinical characteristics analysis of children with Noonan-like syndrome with loose anagen hair

作　　者：王稀欧 刘子勤[1] 上官少方[2] 赖建铭[3] 王鹏超 宋福英[1] 叶雪[1] 杜牧[1] 黄书越 高亢 Wang Xiou;Liu Ziqin;Shangguan Shaofang;Lai Jianming;Wang Pengchao;Song Fuying;Ye Xue;Du Mu;Huang Shuyue;Gao Kang(Department of Endocrinology,Children′s Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China;Department of Genetics,Capital Institute of Pediatrics,Beijing 100020,China;Department of Rheumatology and Immunology,Children′s Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China;Chigene(Beijing)Translational Medical Research Center,Beijing 100176,China)

机构地区：[1]首都儿科研究所附属儿童医院内分泌科,北京100020 [2]首都儿科研究所遗传学研究室,北京100020 [3]首都儿科研究所附属儿童医院风湿免疫科,北京100020 [4]北京智因东方转化医学研究中心有限公司,北京100176

出　　处：《中华儿科杂志》2025年第4期405-410,共6页Chinese Journal of Pediatrics

基　　金：北京市市属医院科研培育计划(PX20231302);首都儿科研究所所级基金(LCPY-2023-27,LCPY-2021-28)。

摘　　要：目的分析努南样综合征伴毛发松动(NS-LAH)患儿的临床及遗传学特征。方法回顾性分析首都儿科研究所内分泌科2018年1月至2024年6月诊断的5例NS-LAH患儿一般情况、临床表现、特殊体征、治疗、预后等临床资料,总结其临床特征,通过全外显子测序联合Sanger测序完成家系遗传学病因分析,变异应用美国医学遗传学与基因组学学会指南进行解读。结果5例NS-LAH患儿中男3例、女2例,诊断年龄为2.3~7.7岁,均因身高增长缓慢就诊。母孕产史、出生史均未见异常。例2、5出生时为巨大儿。5例患儿除具有Noonan综合征特征性面容、身材矮小及不同程度的智力运动发育落后外,均表现为毛发稀疏、易脱落以及大头围。心脏结构异常者4例,其中肥厚型心肌病1例,房间隔缺损2例,卵圆孔未闭1例。4例患儿发现SHOC2基因新生杂合错义变异,其中3例为c.4A>G(p.S2G),1例为c.519G>C(p.M173I)。1例发现PPP1CB基因新生杂合错义变异c.146C>G(p.P49R)。3例患儿诊断生长激素缺乏症,应用人重组生长激素治疗1.7、2.7、0.5年,身高增长11.8、8.4、13.0 cm/年。4例SHOC2基因变异患儿中,2例患系统性红斑狼疮,1例出现不明原因关节炎。结论NS-LAH临床多以生长缓慢就诊,头围增大及毛发稀疏、松动为特征性表现;生长激素缺乏症发生率高,生长激素治疗效果可;SHOC2基因的经典变异(c.4A>G)有发生自身免疫性疾病的风险。Objective To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair(NS-LAH).Methods A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024.This analysis encompassed the patients′demographic information,clinical manifestations,distinguishing features,treatment regimens,and prognostic outcomes to elucidate their clinical characteristics.Additionally,whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families,and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results Among the 5 NS-LAH patients,there were 3 boys and 2 girls,with ages at diagnosis ranging from 2.3 to 7.7 years old.All patients presented with short stature as a primary complaint.Birth histories were generally unremarkable,though case 2 and 5 of macrosomia were noted.In addition to the characteristic facial features of Noonan syndrome,short stature,and varying degrees of intellectual and motor developmental delay,all 5 patients exhibited sparse hair that was easily shed,as well as enlarged head circumferences.Four patients showed structural cardiac abnormalities,which included a case of hypertrophic cardiomyopathy,2 cases of atrial septal defect,and 1 case of patent foramen ovale.Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients,comprising 3 cases with c.4A>G(p.S2G)and one case with c.519G>C(p.M173I).Additionally,one patient was found to have a heterozygous missense variantion c.146C>G(p.P49R)in PPP1CB gene.Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7,2.7 and 0.5 years.This resulted in significant improvements in height,with annual increases of 11.8,8.4 and 13.0 cm,respectively.Among the 4 patients with SHOC2 varian

关 键 词：努南综合征 努南样综合征伴毛发松动 基因 SHOC2 基因 PPP1CB 

分 类 号：R725.9[医药卫生—儿科]