What Was Observed? (Introduction)

• Researchers surveyed 167 pairs of conjoined twins from local cases and literature to study laterality defects.
• Laterality defects refer to abnormal left‐right placement of internal organs, such as the heart being on the wrong side.
• The likelihood of these defects depended on how the twins were physically joined.

What are Laterality Defects?

• They are conditions where the normal left-right arrangement of organs is disrupted.
• For example, a heart that is normally on the left may be reversed to the right.
• This abnormality can affect overall organ function and body symmetry.

Patients and Observations

• Twins joined obliquely at the chest/abdomen (thoracopagus) or laterally at the chest (dicephalus) showed laterality defects in nearly half of the cases (33 out of 69).
• Twin pairs joined only at the head (craniopagus) or pelvis (ischiopagus) did not exhibit laterality defects (0 out of 98 cases).
• In affected twins, the right-side twin was most frequently the one with the defect (86% in dicephalus and 71% in thoracopagus cases).

Understanding the Mechanism (Case Reports – Simplified)

• During early embryonic development (gastrulation), specific signals establish the left-right differences in the body.
• Key signals involved:
  • Activin: A substance produced on the right side that normally suppresses a gene called Sonic hedgehog (Shh) on that same side.
  • Sonic hedgehog (Shh): Typically active on the left, it triggers the production of another signal called nodal, which helps set the heart’s position.
  • Nodal: A signal that ensures organs like the heart develop on the correct side.
• If conjoined twins form from two parallel primitive streaks (an early organizing region in the embryo), the activin from one twin can cross over and inhibit Shh in the other twin.
• This cross-signaling leads to the affected twin (usually the right-side twin) lacking Shh expression in the node, resulting in random or reversed heart placement.
• If the primitive streaks are angled rather than perfectly parallel, the signals may mix in different ways. For example, one twin might end up with double-sided nodal expression, again causing abnormal organ placement.
• Imagine two chefs working in adjacent kitchens (the primitive streaks) that are too close; if ingredients (signals) spill over from one kitchen to the other, the final dishes (organ development) can get mixed up.

Key Conclusions (Discussion)

• Laterality defects in conjoined twins are linked to the orientation and proximity of their primitive streaks during early development.
• Twin pairs joined at the chest or abdomen are at higher risk because their developmental signals can interfere with each other.
• The study draws on experiments in chick embryos where similar signals (activin, Shh, and nodal) control left-right asymmetry, providing a model for understanding human conjoined twins.
• Normally, a barrier prevents signals from crossing over, but in conjoined twins this barrier may be compromised, leading to mixed or reversed signals.
• This research helps explain why only certain types of conjoined twins exhibit laterality defects.

Acknowledgements and Additional Information

• The study was made possible through contributions from multiple experts and institutions, combining clinical data on conjoined twins with experimental insights from chick embryology.
• It builds on earlier models and research, deepening our understanding of the complex process of left-right organ development.

观察到了什么？ (引言)

• 研究人员调查了167对连体双胞胎，这些数据来自本地病例和文献，以研究左右不对称缺陷。
• 左右不对称缺陷指的是内脏器官的左右排列出现异常，例如心脏出现在错误的一侧。
• 这些缺陷的发生率取决于双胞胎的连接方式。

什么是左右不对称缺陷？

• 这是指器官的正常左右排列被打乱的情况。
• 例如，通常位于左侧的心脏可能会反转到右侧。
• 这种异常会影响器官的整体功能和身体的对称性。

患者和观察

• 在胸部或腹部斜连接（胸腹连体）或胸部侧面连接（双头连体）的双胞胎中，近一半的病例（69例中有33例）出现了一方心脏位置反转的现象。
• 而仅在头部（颅连体）或骨盆（骨盆连体）连接的双胞胎中，并未观察到此类缺陷（98例中为0例）。
• 在受影响的双胞胎中，右侧的双胞胎更常表现出缺陷（在双头连体中86%，在胸腹连体中71%）。

理解机制 (病例报告 – 简化版)

• 在胚胎早期发育阶段（原肠形成期），特定信号帮助建立身体的左右差异。
• 关键信号包括：
  • 激活素 (Activin)：在右侧产生的物质，通常抑制右侧一个叫做Sonic hedgehog (Shh) 的基因。
  • Sonic hedgehog (Shh)：通常在左侧活跃，触发另一种信号——结节 (Nodal) 的产生，决定心脏的位置。
  • 结节 (Nodal)：确保心脏等器官在正确的一侧发育的信号。
• 如果连体双胞胎来自两条平行的原肠板（胚胎早期的重要组织区域），一侧的激活素可能会交叉抑制另一侧的Shh表达。
• 这种交叉信号会导致一方（通常是右侧）的胚胎在胚结处缺乏Shh表达，从而使心脏位置随机或反转。
• 如果原肠板排列成一定角度而非完全平行，信号可能以不同方式混合，例如导致一方出现双侧结节表达，引起器官位置异常。
• 可以把这种情况想象成两个厨房（原肠板）相邻工作，如果厨房之间的隔断（信号屏障）不够牢固，食材（信号）就可能互相混合，导致菜肴（器官发育）出现问题。

主要结论 (讨论)

• 连体双胞胎中的左右不对称缺陷与其早期发育时原肠板的排列方式密切相关。
• 胸部或腹部连接的双胞胎风险更高，因为它们的发育信号更容易互相干扰。
• 该研究利用鸡胚模型来解释这些机制，因为鸟类和人类在左右发育调控中使用类似的信号（激活素、Shh、结节）。
• 在正常发育中，中线屏障会阻止信号交叉，但在连体双胞胎中，这个屏障可能受损，导致信号混乱。
• 这些发现为解释为什么只有特定类型的连体双胞胎会出现左右不对称缺陷提供了新的见解。

致谢及附加信息

• 该研究得到了多位专家和机构的支持，结合了鸡胚实验和连体双胞胎的临床数据。
• 研究基于以往的模型和研究，进一步阐明了胚胎左右发育这一复杂过程。