Diagnosis and management of the phenotypic spectrum of twins with Beckwith-Wiedemann syndrome.
Diagnosis and management of the phenotypic spectrum of twins with Beckwith-Wiedemann syndrome.
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DOI：
10.1002/ajmg.a.61164
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发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Kalish JM
中科院分区：
文献类型：
--
作者：
Cohen JL;Duffy KA;Sajorda BJ;Hathaway ER;Gonzalez-Gandolfi CX;Richards-Yutz J;Gunter AT;Ganguly A;Kaplan J;Deardorff MA;Kalish JM
Beckwith-Wiedemann综合征（BWS）是一种具有异质性表型谱的过度生长障碍。在BWS中，单卵双生的发生率增加。鉴于定义BWS的表观遗传性质和表型谱，双胞胎的临床特征往往不一致，临床医生面临着诊断和管理这些双胞胎的挑战。我们提出了一个队列的多胎妊娠，其中一个或多个孩子从每个怀孕被诊断为BWS。我们对单绒毛膜和绒毛膜妊娠进行了病历回顾。单绒毛膜双胞胎的临床评分显示先证者和双胞胎之间的表型不一致。基于线性回归分析，先证者较高的临床评分与双胞胎兄弟姐妹之间较大的表型不一致性相关。然而，尽管表型不一致，我们还是观察到怀孕的加性临床评分（先证者的评分加上双胞胎怀孕的评分）。这种怀孕受影响程度有限的想法意味着受表观遗传影响的细胞数量有限。这进一步证实了这样的想法，即单卵单绒毛膜双胞胎的时间与建立和/或维持印记的中断。先证者和其双胞胎之间临床评分的差异可能是由于弥散镶嵌现象，即在单卵单绒毛膜妊娠的多个胎儿中受影响细胞的不对称分布，导致一系列受影响的表型。基于这些发现，我们推荐了一种保守的方法来临床评估所有受BWS影响的单卵多胎妊娠儿童的算法。
Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with a heterogeneous phenotypic spectrum. There is an increased prevalence of monozygotic twinning in BWS. Given the epigenetic nature and phenotypic spectrum that defines BWS, twins are often discordant for clinical features, and clinicians are faced with the challenge of diagnosing and managing these twins. We present a cohort of multiple pregnancies in which one or more child from each pregnancy was diagnosed with BWS. We conducted a chart review of monochorionic and dichorionic gestations. Clinical scores for monochorionic twins demonstrated phenotypic discordance between the proband and twin. Based on linear regression analysis, a higher clinical score in the proband correlated with larger phenotypic discordance between twin siblings. Despite phenotypic discordance, however, we observed a consistent additive clinical score for a pregnancy (proband’s plus twin’s scores from a pregnancy). This idea of a finite degree of affectedness for a pregnancy implies a finite number of epigenetically affected cells. This further corroborates the idea that timing of monozygotic monochorionic twinning correlates with the disruption of establishment and/or maintenance of imprinting. The difference in clinical score between a proband and their twin may be due to diffused mosaicism, whereby there is an asymmetric distribution of affected cells among the multiple fetuses in a monozygotic monochorionic pregnancy, leading to a spectrum of variably affected phenotypes. Based on these findings, we recommend an algorithm for a conservative approach to clinically evaluate all children in a monozygotic multiple gestation affected by BWS.
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DOI：
10.1002/ajmg.1320420440
发表时间：
1992-02-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
CLAYTONSMITH, J;READ, AP;DONNAI, D
通讯作者：
DONNAI, D
影响因子：
4
作者：
Hall, JG
通讯作者：
Hall, JG
DOI：
10.1002/ajmg.c.30058
发表时间：
2005-08-15
影响因子：
3.1
作者：
Weksberg, R;Shuman, C;Smith, AC
通讯作者：
Smith, AC
影响因子：
5.2
作者：
Bliek, Jet;Alders, Marielle;Mannens, Marcel M. A. M.
通讯作者：
Mannens, Marcel M. A. M.
影响因子：
3.5
作者：
Weksberg, R;Shuman, C;Squire, J
通讯作者：
Squire, J