Singh Amit, Pajni Ketan, Panigrahi Inusha, Khetarpal Preeti
Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Department of Paediatric Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Curr Pediatr Rev. 2023;19(2):157-168. doi: 10.2174/1573396318666220315142542.
Silver-Russell syndrome (SRS) is a developmental disorder involving extreme growth failure, characteristic facial features and underlying genetic heterogeneity. As the clinical heterogeneity of SRS makes diagnosis a challenging task, the worldwide incidence of SRS could vary from 1:30,000 to 1:100,000. Although various chromosomal, genetic, and epigenetic mutations have been linked with SRS, the cause had only been identified in half of the cases.
To have a better understanding of the SRS clinical presentation and mutation/ epimutation responsible for SRS, a systematic review of the literature was carried out using appropriate keywords in various scientific databases (PROSPERO protocol registration CRD42021273211). Clinical features of SRS have been compiled and presented corresponding to the specific genetic subtype. An attempt has been made to understand the recurrence risk and the role of model organisms in understanding the molecular mechanisms of SRS pathology, treatment, and management strategies of the affected patients through the analysis of selected literature.
156 articles were selected to understand the clinical and molecular heterogeneity of SRS. Information about detailed clinical features was available for 228 patients only, and it was observed that body asymmetry and relative macrocephaly were most prevalent in cases with methylation defects of the 11p15 region. In about 38% of cases, methylation defects in ICRs or genomic mutations at the 11p15 region have been implicated. Maternal uniparental disomy of chromosome 7 (mUPD7) accounts for about 7% of SRS cases, and rarely, uniparental disomy of other autosomes (11, 14, 16, and 20 chromosomes) has been documented. Mutation in half of the cases is yet to be identified. Studies involving mice as experimental animals have been helpful in understanding the underlying molecular mechanism. As the clinical presentation of the syndrome varies a lot, treatment needs to be individualized with multidisciplinary effort.
SRS is a clinically and genetically heterogeneous disorder, with most of the cases being implicated with a mutation in the 11p15 region and maternal disomy of chromosome 7. Recurrence risk varies according to the molecular subtype. Studies with mice as a model organism have been useful in understanding the underlying molecular mechanism leading to the characteristic clinical presentation of the syndrome. Management strategies often need to be individualized due to varied clinical presentations.
Silver-Russell综合征（SRS）是一种发育障碍性疾病，其特征为极度生长迟缓、特殊面容以及潜在的基因异质性。由于SRS的临床异质性使得诊断颇具挑战性，SRS在全球的发病率可能在1:30000至1:100000之间。尽管多种染色体、基因及表观遗传突变都与SRS相关，但仅在半数病例中明确了病因。
为了更好地了解SRS的临床表现以及导致SRS的突变/表观突变，我们在多个科学数据库中使用恰当的关键词进行了系统的文献综述（PROSPERO方案注册号CRD42021273211）。已汇总SRS的临床特征，并根据特定的基因亚型进行了呈现。通过对所选文献的分析，试图了解复发风险以及模式生物在理解SRS病理分子机制、治疗及对受影响患者的管理策略方面的作用。
选取了156篇文章来了解SRS的临床和分子异质性。仅228例患者有详细的临床特征信息，且观察到身体不对称和相对巨头畸形在11p15区域甲基化缺陷的病例中最为常见。约38%的病例与ICR中的甲基化缺陷或11p15区域的基因组突变有关。7号染色体单亲二体（mUPD7）约占SRS病例的7%，其他常染色体（11、14、16和20号染色体）的单亲二体情况则鲜有报道。半数病例的突变尚未明确。以小鼠作为实验动物的研究有助于理解潜在的分子机制。由于该综合征的临床表现差异很大，治疗需要多学科协作进行个体化处理。
SRS是一种临床和遗传异质性疾病，大多数病例与11p15区域的突变及7号染色体单亲二体有关。复发风险因分子亚型而异。以小鼠作为模式生物的研究有助于理解导致该综合征特征性临床表现的潜在分子机制。由于临床表现多样，管理策略通常需要个体化。
