Abstract：
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a phenotypically and genetically heterogeneous disorder associated with epigenetic/genetic aberrations on chromosome 11p15.4p15.5. There is no consensus criterion for prenatal diagnosis of BWS.
METHODS: Three BWS patients with their clinical histories, prenatal ultrasonographic features, and results of molecular diagnosis were presented. Likewise, by incorporating the findings of our cases and literature review, the phenotypic spectrum and genotype-phenotype correlations of fetal BWS were summarized, and a practical approach in prenatal diagnosis of BWS was proposed.
RESULTS: A total of 166 BWS cases with prenatal features were included for analysis. Common fetal features include abdominal wall defects (42.8%), polyhydramnios (33.1%), and macrosomia (32.5%). Molecular pathologies include methylation changes in imprinting control region 1 and 2 (ICR1 and ICR2), paternal uniparental disomy of chromosome 11p15.5, copy number change involving 11p15, etc. Some genotype-phenotype correlations were observed. However, the broad phenotypic spectrum but limited features manifested by affected fetuses rendering ultrasonographic diagnosis not easy.
CONCLUSIONS: Molecular tests are used for prenatal diagnosis of BWS suspected by ultrasonography. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is recommended as the first-line molecular tool because it simultaneously detects ICR1/ICR2 methylation statuses and copy numbers that solve the majority of clinical cases in the prenatal scenario.
METHODS: Three BWS patients with their clinical histories, prenatal ultrasonographic features, and results of molecular diagnosis were presented. Likewise, by incorporating the findings of our cases and literature review, the phenotypic spectrum and genotype-phenotype correlations of fetal BWS were summarized, and a practical approach in prenatal diagnosis of BWS was proposed.
RESULTS: A total of 166 BWS cases with prenatal features were included for analysis. Common fetal features include abdominal wall defects (42.8%), polyhydramnios (33.1%), and macrosomia (32.5%). Molecular pathologies include methylation changes in imprinting control region 1 and 2 (ICR1 and ICR2), paternal uniparental disomy of chromosome 11p15.5, copy number change involving 11p15, etc. Some genotype-phenotype correlations were observed. However, the broad phenotypic spectrum but limited features manifested by affected fetuses rendering ultrasonographic diagnosis not easy.
CONCLUSIONS: Molecular tests are used for prenatal diagnosis of BWS suspected by ultrasonography. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is recommended as the first-line molecular tool because it simultaneously detects ICR1/ICR2 methylation statuses and copy numbers that solve the majority of clinical cases in the prenatal scenario.
摘要：
背景：Beckwith-Wiedemann综合征（BWS）是一种表型和遗传异质性疾病，与染色体11p15.4p15.5上的表观遗传/遗传畸变有关。BWS的产前诊断尚无共识标准。
方法：三名有临床病史的BWS患者，产前超声特征，并给出了分子诊断结果。同样，通过结合我们案例的发现和文献综述，总结了胎儿BWS的表型谱和基因型-表型相关性，并提出了一种实用的BWS产前诊断方法。
结果：共纳入166例具有产前特征的BWS病例进行分析。常见的胎儿特征包括腹壁缺损（42.8％），羊水过多（33.1%），巨大儿(32.5%)。分子病理学包括印迹控制区1和2（ICR1和ICR2）的甲基化变化，染色体11p15.5的父系单亲二体性，涉及11p15的拷贝数变化等。观察到一些基因型-表型相关性。然而,广泛的表型谱，但受影响的胎儿表现出有限的特征，使得超声诊断不容易。
结论：分子检测用于超声检查怀疑的BWS的产前诊断。甲基化特异性多重连接依赖性探针扩增（MS-MLPA）被推荐作为一线分子工具，因为它同时检测ICR1/ICR2甲基化状态和拷贝数，解决了产前情况下的大多数临床病例。
方法：三名有临床病史的BWS患者，产前超声特征，并给出了分子诊断结果。同样，通过结合我们案例的发现和文献综述，总结了胎儿BWS的表型谱和基因型-表型相关性，并提出了一种实用的BWS产前诊断方法。
结果：共纳入166例具有产前特征的BWS病例进行分析。常见的胎儿特征包括腹壁缺损（42.8％），羊水过多（33.1%），巨大儿(32.5%)。分子病理学包括印迹控制区1和2（ICR1和ICR2）的甲基化变化，染色体11p15.5的父系单亲二体性，涉及11p15的拷贝数变化等。观察到一些基因型-表型相关性。然而,广泛的表型谱，但受影响的胎儿表现出有限的特征，使得超声诊断不容易。
结论：分子检测用于超声检查怀疑的BWS的产前诊断。甲基化特异性多重连接依赖性探针扩增（MS-MLPA）被推荐作为一线分子工具，因为它同时检测ICR1/ICR2甲基化状态和拷贝数，解决了产前情况下的大多数临床病例。
