Several recurrent malformation associations affecting the development of the embryo have been described in which a genetic etiology has not been found, including LBWC, MURCS, OAVS, OEIS, POC, VACTERL, referred to here as “recurrent constellations of embryonic malformations” (RCEM). All are characterized by an excess of reported monozygotic discordant twins and lack of familial recurrence. We performed a comprehensive review of published twin data across all six phenotypes to allow a more robust assessment of the association with twinning and potential embryologic timing of a disruptive event. We recorded the type of twinning, any overlapping features of another RCEM, maternal characteristics, and the use of ART. Statistically significant associations included an excess of monozygotic twins and 80% discordance rate for the phenotype across all twins. There was an 18.5% rate of ART and no consistently reported maternal adverse events during pregnancy. We found 24 instances of co‐occurrence of two RCEM, suggesting a shared pathogenesis across all RCEM phenotypes. We hypothesize the following timing for RCEM phenotypes from the earliest perturbation in development to the latest: LBWC, POC, OEIS, VACTERL, OAVS, then MURCS. The RCEM group of conditions should be considered a spectrum that could be studied as a group.

中文翻译：

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胚胎畸形的复发星座被重新概念化为具有共同发病机制的一组重叠疾病。

已经描述了几种影响胚胎发育的复发性畸形关联，其中未发现遗传病因，包括LBWC，MURCS，OAVS，OEIS，POC，VACTERL，在此称为“胚胎畸形复发星座”（RCEM） 。所有这些患者的特征都是报告的单卵双歧不一致双胞胎过多，且家族性复发缺乏。我们对所有六种表型的已发表双胞胎数据进行了全面审查，以对与孪生和破坏性事件的潜在胚胎学时机的关联进行更可靠的评估。我们记录了孪生的类型，另一个RCEM的任何重叠特征，母体特征以及ART的使用。具有统计意义的关联包括单卵双胞胎过多和所有双胞胎的表型不一致率达80％。妊娠期间ART的发生率为18.5％，并且没有持续报道孕产妇不良事件。我们发现两种RCEM并存的24个实例，表明所有RCEM表型都有共同的发病机制。我们假设从最早的扰动到最新的扰动，RCEM表型的出现时间如下：LBWC，POC，OEIS，VACTERL，OAVS，然后是MURCS。RCEM组条件应视为可以作为一组进行研究的光谱。从最早的扰动到最新的扰动，我们假设RCEM表型的时序如下：LBWC，POC，OEIS，VACTERL，OAVS，然后是MURCS。RCEM组条件应视为可以作为一组进行研究的光谱。我们假设从最早的扰动到最新的扰动，RCEM表型的出现时间如下：LBWC，POC，OEIS，VACTERL，OAVS，然后是MURCS。RCEM组条件应视为可以作为一组进行研究的光谱。