Rare Diseases Research Group. Molecular (Epi)Genetics Laboratory, BioAraba Health Research Institute, OSI Araba University Hospital, Vitoria-Gasteiz, Araba, Spain.
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Araba, Spain.
BMC Med Genomics. 2018 Dec 27;11(1):124. doi: 10.1186/s12920-018-0441-z.
Silver-Russell Syndrome (SRS) is a rare growth-related genetic disorder mainly characterized by prenatal and postnatal growth failure. Although molecular causes are not clear in all cases, the most common mechanisms involved in SRS are loss of methylation on chromosome 11p15 (≈50%) and maternal uniparental disomy for chromosome 7 (upd(7)mat) (≈10%).
We present a girl with clinical suspicion of SRS (intrauterine and postnatal growth retardation, prominent forehead, triangular face, mild psychomotor delay, transient neonatal hypoglycemia, mild hypotonia and single umbilical artery). Methylation and copy number variations at chromosomes 11 and 7 were studied by methylation-specific multiplex ligation-dependent probe amplification and as no alterations were found, molecular karyotyping was performed. A deletion at 5p15.33p15.2 was identified (arr[GRCh37] 5p15.33p15.2(25942-11644643)× 1), similar to those found in patients with Cri-du-chat Syndrome (CdCS). CdCS is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-), whose main feature is a high-pitched mewing cry in infancy, accompanied by multiple congenital anomalies, intellectual disability, microcephaly and facial dysmorphism.
The absence of some CdCS features in the current patient could be due to the fact that in her case the critical regions responsible do not lie within the identified deletion. In fact, a literature review revealed a high degree of concordance between the clinical manifestations of the two syndromes.
银-罗素综合征（SRS）是一种罕见的与生长相关的遗传性疾病，主要表现为产前和产后生长发育迟缓。尽管并非所有病例的分子病因都明确，但 SRS 最常见的涉及机制是 11 号染色体 11p15 去甲基化（≈50%）和 7 号染色体母源单亲二体性（upd(7)mat）（≈10%）。
我们报告了一名有 SRS 临床可疑表现的女孩（宫内和产后生长迟缓、前额突出、三角脸、轻度精神运动发育迟缓、短暂性新生儿低血糖、轻度肌张力低下和单脐动脉）。通过甲基化特异性多重连接依赖性探针扩增检测 11 号和 7 号染色体的甲基化和拷贝数变化，由于未发现改变，因此进行了分子核型分析。鉴定出 5p15.33p15.2 缺失（arr[GRCh37] 5p15.33p15.2(25942-11644643)× 1），与猫叫综合征（CdCS）患者的缺失相似。CdCS 是一种遗传性疾病，由 5 号染色体短臂（5p-）上大小不定的缺失引起，其主要特征是婴儿期高音猫叫样哭声，伴有多种先天性异常、智力障碍、小头畸形和面部畸形。
目前患者缺乏一些 CdCS 特征可能是因为导致这些特征的关键区域不在已确定的缺失区内。实际上，文献回顾显示这两种综合征的临床表现高度一致。
