Silver-Russell syndrome
Silver-Russell syndrome
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DOI：
10.1016/j.beem.2010.06.005
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发表时间：
2011-02-01
影响因子：
7.4
通讯作者：
Kannenberg, Kai
中科院分区：
文献类型：
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作者：
Binder, Gerhard;Begemann, Matthias;Kannenberg, Kai
Silver-Russell综合征（SRS）是一种散发性的临床和遗传异质性疾病。诊断是基于以下特征的变量组合：宫内发育迟缓，身材矮小，因为缺乏追赶性生长，体重不足，相对大头畸形，典型的三角脸，身体不对称和几个轻微的异常，包括斜指V。检测到的主要遗传缺陷是在表观遗传水平上：约44%的病例中11 p15上的印记控制区1（ICR 1）的低甲基化，以及5-10%的病例中7号染色体的母体单亲二体性（UPD（7）mat）。严重表型通常与ICR 1的低甲基化相关，而轻度表型更常见于与UPD（7）mat结合。这些表位突变的起源和生物学后果仍然不清楚。对于基因检测，我们建议对7 p和7 q基因座进行甲基化特异性PCR方法（通过微卫星分型确认）以检测UPD（7）mat，并对11 p15基因座进行甲基化特异性多重连接依赖探针扩增（MS-MLPA）方法。SRS中的身材矮小可以通过使用药理学剂量的重组GH治疗，导致良好的短期追赶;关于最终身高的治疗效果的充分信息仍然缺失。(C)2010爱思唯尔有限公司版权所有。
The Silver-Russell syndrome (SRS) is a sporadic clinically and genetically heterogeneous disorder. Diagnosis is based on the variable combination of the following characteristics: intrauterine growth retardation, short stature because of lack of catch-up growth, underweight, relative macrocephaly, typical triangular face, body asymmetry and several minor anomalies including clinodactyly V. Different diagnostic scores have been proposed. The main genetic defects detected are at the epigenetic level: hypomethylation of the imprinting control region 1 (ICR1) on 11p15 in around 44% of cases and maternal uniparental disomy of chromosome 7 (UPD(7)mat) in 5-10% of cases. Severe phenotype is frequently associated with hypomethylation of ICR1 while mild phenotype is more often seen in combination with UPD(7)mat. Origins and biological consequences of these epimuations are still obscure. For genetic testing, we recommend a methylation-specific PCR-approach for both 7p and 7q loci (confirmed by microsatellite typing) for the detection of UPD(7)mat, and the methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) approach for methylation analysis of the 11p15 loci. Short stature in SRS can be treated by use of pharmacological doses of recombinant GH resulting in good short-term catch-up; sufficient information on the therapeutic effect in terms of final height is still missing. (C) 2010 Elsevier Ltd. All rights reserved.