中国循证儿科杂志 ›› 2019, Vol. 14 ›› Issue (4): 282-286.DOI: 10.3969/j.issn.1673-5501.2019.04.007

• 论著 • 上一篇    下一篇

Russel Silver综合征19例病例系列报告

张萍1,4, 刘仁超1,4, 陆炜2, 吴冰冰1, 王慧君3, 周文浩3   

  1. 1 复旦大学附属儿科医院儿科研究所 上海,201102;
    2 复旦大学附属儿科医院内分泌遗传代谢科 上海,201102;
    3 上海市出生缺陷防治重点实验室,复旦大学儿童发育与疾病转化医学研究中心,卫生部新生儿疾病重点实验室,复旦大学附属儿科医院 上海,201102;
    4 共同第一作者
  • 收稿日期:2019-07-26 修回日期:2019-08-22 出版日期:2019-08-25 发布日期:2019-08-25
  • 通讯作者: 周文浩,E-mail:zwhchfu@126.com;王慧君,E-mail:huijunwang@fudan.edu.cn

Clinical analysis of 19 children with Russel Silver syndrome

ZHANG Ping1,4, LIU Ren-chao1,4, LU Wei2, WU Bing-bing1, WANG Hui-jun3, ZHOU Wen-hao3   

  1. 1 Institue of Pediatrics, Children's Hospital of Fudan University,Shanghai 201102;
    2 Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University,Shanghai 201102;
    3 Shanghai Key Laboratory of Birth Defects,The Translational Medicine Center of Children Development and Disease of Fudan University, Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University,Shanghai 201102;
    4 Co-first author
  • Received:2019-07-26 Revised:2019-08-22 Online:2019-08-25 Published:2019-08-25
  • Contact: ZHOU Wen-hao,E-mail: zwhchfu@126.com; WANG Hui-jun, E-mail:huijunwang@fudan.edu.cn

摘要: 目的 总结分析经甲基化特异性多重链接探针扩增技术(MS-MLPA)确诊的Russel Silver综合征(RSS)患儿的临床特征、基因型(表观突变)以及表型和基因型的相关性,旨在提升对该病的认识。方法 收集2015年1月1日至2019年6月30日复旦大学附属儿科医院(我院)分子医学中心经MS-MLPA确诊的RSS连续病例的临床资料。MS-MLPA行11p15区域甲基化和拷贝数变异(CNV)情况检测,应用GeneMarker软件对实验数据进行均一化处理及结果判读。结果 19例RSS患儿,女8例,男11例,确诊年龄中位数3.3岁(3月龄至10岁)。小于胎龄儿18例,就诊时18例患儿身高均低于同龄儿童身高P3,体重均低于同龄儿童体重P10。特殊面容发生率较高的表型有前额突出9例,三角脸7例,肢体不对称和手指短或内侧弯曲6例,小下颌5例。其他表现包括眼距宽、低耳位、高腭弓、牙齿突出、胸廓畸形、脊柱侧凸和房间隔缺损等。19例RSS患儿有3例检测到携带11p15区域拷贝数重复,余16例均显示H19-DMR低甲基化且无CNV。结论 有宫内和出生后生长发育迟缓、肢体不对称和特殊面容的儿童,应注意RSS的可能,首选MS-MLPA检测,以利于及早干预和遗传咨询。

关键词: Russel Silver综合征, 甲基化特异性多重链接探针扩增技术, 临床特征, 基因型(表观突变)

Abstract: Objective To analyze the clinical characteristics, genotype (epimutation), and the correlation between phenotype and genotype of children with Russel Silver syndrome (RSS) diagnosed by methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) to improve the understanding of the disease.Methods RSS patients were enrolled from the Molecular Medicine Center of Children's Hospital of Fudan University from January 2015 to June 2019. MS-MLPA was used for the detection of 11p15 methylation level and copy number variations, and GeneMarker software was used to analyze the experimental data. The correlationship between the phenotype and genotype of RSS was analyzed using Fisher exact test.Results Nineteen RSS patients were diagnosed by MS-MLPA, including 8 females and 11 males, with a median age of 3.3 years (3 months to 10 years). The presence of small for gestational age (SGA) was identified in 18 cases. The height and weight of 18 children were lower than P3 and P10 of the same age, respectively. The common craniofacial features include frontal bossing (9 cases), triangular face (7 cases), body asymmetry (6 cases), short or curved fingers (6 cases) and micrognathia (5 cases). Patients also presented with hypertelorism, low-set ears, high palate, irregular teeth, thoracic deformity, scoliosis and atrial septal defect. There were 3 cases with 11p15 duplication and hypomethylation of H19 differentially methylated region (DMR), while the remaining 16 cases all showed H19-DMR hypomethylation without CNV abnormality.Conclusion MS-MLPA can provide the basis for accurate diagnosis of RSS and thus be helpful for appropriate treatment and family genetic counseling.

Key words: Russel Silver syndrome, Methylation-specific multiplex ligation-dependent probe amplification, Clinical characteristics, Genotype(epimutation)