摘要
目的分析以矮身材为主诉的Noonan综合征(NS)的分子遗传学和临床表型的特点,为以矮身材为主诉就诊的儿童期NS筛查提供临床筛查证据。方法回顾性分析2016年1月至2023年4月在江西省儿童医院内分泌遗传代谢科以矮身材为主诉就诊的14例NS相关基因变异结果和临床表型特点、重组人生长激素治疗和随访情况,并通过文献检索比较变异表型的差异。结果14例患儿中PTPN11基因突变最为常见(11/14例,78.5%),其他基因变异为KRAS、SOS1、RIT1突变各1例;PTPN11基因突变以外显子7最为常见(4/11例,占36.3%)。14例患儿基因突变12例(85.7%)为新发变异,2例(14.3%)为家族遗传,突变类型均为错义突变。14例患儿平均就诊年龄为(7.89±3.65)岁,临床表型主要为严重生长发育迟缓[100%,身高标准差(HtSDS)为(-4.28±1.04)SDS]、骨龄落后[100%,平均落后(2.79±1.11)岁]。12例(85.7%)有特殊面容、10例(71.4%)伴全面发育迟缓、7例(50.0%)伴先天性心脏病(以房间隔缺损最为常见)、7例(50.0%)伴骨骼畸形;5例(35.7%)伴泌尿生殖器异常。其他临床表型包括3例(21.4%)伴眼睑下垂、2例(14.3%)皮肤可见黑色素痣、2例(14.3%)为低出生体重儿,1例伴皮肤血管瘤。5例(38.5%)垂体MRI提示垂体细小。13例患儿进行生长激素激发试验结果提示,1例为生长激素完全缺乏,5例为生长激素部分缺乏;4例接受了重组人生长激素(rhGH)治疗且治疗1.5~2.0年,生长速率均在7~10 cm·年^(-1),未见不良反应。结论以矮小为主要临床症状在内分泌就诊的NS患儿主要表现为出生后严重矮小,部分可无典型NS面容、部分无心脏畸形或仅表现为房间隔缺损,易导致漏诊。因此,以严重生长发育迟缓合并特殊面容的患儿就诊,建议进行遗传学检测明确病因。
Objective To analyze the characteristics of molecular genetics and clinical phenotype of Noonan syndrome(NS)in which short stature is the main complaint,and to provide clinical evidence for screening NS in childhood with short stature as main complaint.Methods The results of NS-related gene variation,clinical phenotypic characteristics,recombinant human growth hormone treatments and follow-ups were retrospectively analyzed in 14 patients with short stature who were admitted to the Department of Endocrinology,Genetics and Metabolism of Jiangxi Children’s Hospital from January 2016 to April 2023,and the differences of variant phenotypes were compared by literature search.Results PTPN11 gene mutation was the most common in 14 children(11/14 cases,78.5%);the other gene variant were KRAS,with 1 case of SOS1 and RIT1 mutation;PTPN11 gene mutations in exon 7 were most common(4/11 cases,36.3%).12 of the 14 gene mutations were new mutations(85.7%)and two(14.3%)were family inherited mutations;all the mutation types were missense mutations.The mean age of the 14 patients was(7.89±3.65)years,and the clinical phenotypes were mainly severe growth retardation[100%,mean height standard deviation(HtSDS)was(-4.28±1.04)SDS],and backwardness in bone age[100%,mean backwardness(2.79±1.11)years].12 cases(85.7%)had specific facial features;10 cases(71.4%)were associated with total growth retardation;7 cases(50.0%)with congenital heart disease(atrial septal defect was the most common);7 cases(50.0%)with skeletal malformation;5 cases(35.7%)with urogenital anomalies.Other clinical phenotypes included eyelid ptosis in 3 cases(21.4%),visible skin nevus in 2 cases(14.3%),low birth weight in 2 cases(14.3%),and cutaneous hemangioma in 1 case.The pituitary gland MRI suggested the miniaturization of pituitary gland in 5 cases(38.5%).From growth hormone stimulation tests in 13 cases,1 case was completely growth hormone deficient;5 cases were partially growth hormone deficient;4 cases were treated with recombinant human growth hormone(rhGH)for
作者
黄慧
杨玉
杨利
谢理玲
张东光
陈卡
帅霞
熊翔宇
徐磊
HUANG Hui;YANG Yu;YANG Li;XIE Li-ling;ZHANG Dong-guang;CHEN Ka;SHUAI Xia;XIONG Xiang-yu;XU Lei(Jiangxi Provincial Key Laboratory of Child Development and Genetics;Department of Endocrinology,Metabolism and Genetics,Jiangxi Provincial Children’s Hospital;Jiangxi Provincial Children’s Genetic and Metabolic Disease Clinical Medical Research Center,Nanchang 330006,China)
出处
《实用临床医学（江西）》
CAS
2024年第2期44-49,共6页
Practical Clinical Medicine
基金
江西省卫健委科技计划项目(202110099)。
