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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (4): 500-505    DOI: 10.3724/zdxbyxb-2021-0263
    
Clinical features, genetic detection and therapeutic response to rhGH of children with Noonan syndrome: an analysis of 12 cases
SHANGGUAN Huakun(),XU Yuanbin,CHEN Ruimin()
Department of Endocrine Genetics and Metabolism, Fuzhou Children’ Hospital of Fujian Medical University, Fuzhou 350001, China
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Abstract  

Objective:To analyze the clinical manifestations, genetic features and therapeutic efficacy of patients with Noonan syndrome (NS). Methods:The clinical data of 12 NS children treated in Fuzhou Children’ Hospital of Fujian Medical University from September 2015 to April 2021 were analyzed. Among them, 7 patients with height lower than two standard deviations of the mean (or below the third percentile) were treated with recombinant human growth hormone (rhGH), and were followed up every 3?months.Results:The clinical characteristics were as following: facial anomalies (n=12), short stature (n=11), congenital heart diseases (n=5), facial freckles (n=4), coffee spots on the skin (n=3), intelligence disability (n=3),cryptorchidism (n=3), feeding difficulties (n=2), scoliosis (n=2), pectus carinatum (n=2), pectus excavatum (n=1), rib dysplasia companied with short finger (n=1), hyperopia (n=1), myopia (n=1) and early puberty (n=1). ThePTPN11 mutation was detected in 10 cases, RIT1 mutation was detected in 1 case, and RAF1 mutation was detected in 1 case. In 7 patients treated with rhGH, the mean height velocity increased from (2.8±1.0)?cm/year before treatment to (8.3±1.6)?cm/year after treatment for (1.5±0.8)?years (P<0.01); the height velocity was the fastest during 3 to 6?months of treatment, and then gradually went slower. The serum levels of insulin-like growth factor 1 (IGF-1) remained within the normal range.Conclusions:The clinical manifestations of NS are diverse, and the disease can be diagnosed through genetic testing. For NS patients with short stature, rhGH treatment can increase the height velocity and no obvious adverse reactions were found.



Key wordsNoonan syndrome      Gene mutation      Short stature      Early puberty      Treatment outcome      Follow-up studies     
Received: 11 May 2021      Published: 01 November 2021
CLC:  R596  
Corresponding Authors: CHEN Ruimin     E-mail: 1249652614@qq.com;chenrm321@sina.com
Cite this article:

SHANGGUAN Huakun,XU Yuanbin,CHEN Ruimin. Clinical features, genetic detection and therapeutic response to rhGH of children with Noonan syndrome: an analysis of 12 cases. J Zhejiang Univ (Med Sci), 2021, 50(4): 500-505.

URL:

http://www.zjujournals.com/med/10.3724/zdxbyxb-2021-0263     OR     http://www.zjujournals.com/med/Y2021/V50/I4/500


12例努南综合征患儿的临床特征及重组人生长激素疗效观察

目的:探讨努南综合征患儿的临床表现和遗传学特点,总结重组人生长激素的治疗效果。方法:收集2015年9月至2021年4月就诊于福建医科大学附属福州儿童医院经基因检测确诊的12例努南综合征患儿的资料。以身高低于2个标准差或第3百分位为身材矮小的评判标准,对7例患儿进行重组人生长激素(rhGH)治疗,每3个月随访一次。结果:12例患儿均表现为特殊面容,身材矮小11例,先天性心脏病5例,面部雀斑4例,咖啡斑3例,智力障碍3例,隐睾3例,喂养困难2例,骨骼畸形包括脊柱侧弯2例、鸡胸2例、漏斗胸1例,肋骨发育不良合并短指1例,远视1例,近视1例,青春发育期提前1例。基因检测结果显示,10例患儿携带PTPN11基因突变,1例患儿携带RIT1基因突变,1例患儿携带RAF1基因突变,所有突变均分类为致病性或可能致病性。7例患儿rhGH平均治疗时间为(1.5±0.8)年。与治疗前比较,rhGH治疗后患儿生长速率增加[治疗前(2.8±1.0)cm/年,治疗后(8.3±1.6)cm/年,P<0.01],治疗3~6个月时生长速率最大,此后随着治疗时间的延长生长速率逐渐减小。7例患儿治疗期间胰岛素样生长因子1水平较治疗前均增加,但仍维持在正常范围。结论:努南综合征临床表型谱广,涉及全身多个系统,基因检测可明确诊断。身材矮小的努南综合征患儿rhGH治疗可提高生长速率、改善身高,且治疗期间未见明显不良反应。


关键词: 努南综合征,  基因突变,  身材矮小症,  青春发育期提前,  治疗结果,  随访研究 

例序

基因型

核苷酸位点

氨基酸位点

来源

致病评级

1

PTPN11

c.1529A>G

p.Q510R

母亲

致病

2

PTPN11

c.844A>G

p.I282V

父亲

致病

3

PTPN11

c.184T>G

p.Y62D

新发

致病

4

PTPN11

c.794G>A

p.R265Q

新发

致病

5

PTPN11

c.1508G>A

p.G503E

新发

致病

6

PTPN11

c.188A>G

p.Y63C

新发

致病

7

PTPN11

c.188A>G

p.Y63C

新发

致病

8

RIT1

c.270G>A

p.M90I

未验证

可能致病

9

PTPN11

c.922A>G

p.N308D

父亲

致病

10

PTPN11

c.836A>G

p.Y279C

新发

致病

11

PTPN11

c.922A>G

p.N308D

未验证

可能致病

12

RAF1

c.770C>T

p.S257L

新发

致病

Table 1 Gene mutations in 12 patients with Noonan syndrome
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