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Purpose of Review <p>The association of left-right (LR) axis development with congenital heart disease (CHD).</p> Recent Findings <p>CHD affects up to 1.2% of the population, with 3–7% of cases attributed to abnormal LR patterning. Despite this, disruption of LR axis development remains poorly understood. Here, we examine the molecular mechanisms of embryonic LR axis formation. We review novel findings about LR asymmetry genes, the role of cilia and the nodal flow. We debate whether flow-sensing is based on morphogens or involves mechanosensing and explore mechanisms involved in asymmetric morphogenesis of the heart, including the NODAL-PITX2 cassette, intrinsic cellular chirality, and cardiac neural crest cells. Finally, we discuss environmental factors affecting LR axis formation and the potential development of therapeutics.</p> Summary <p>Understanding the genetic underpinnings of LR axis development and its effects on CHD is crucial for risk stratification of patients, leading to more effective treatment.</p>

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The Role of Left-Right Asymmetry in Congenital Heart Defects: Taking the Right Turn

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月30日

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  • Xavier Da Silva Anjos Machado,
  • Rose Maria Francis,
  • Kamya Mandhar,
  • Sajanika Perinparajah,
  • Srisiddharth Sarma Yadati,
  • Thomas Brand

摘要

Purpose of Review

The association of left-right (LR) axis development with congenital heart disease (CHD).

Recent Findings

CHD affects up to 1.2% of the population, with 3–7% of cases attributed to abnormal LR patterning. Despite this, disruption of LR axis development remains poorly understood. Here, we examine the molecular mechanisms of embryonic LR axis formation. We review novel findings about LR asymmetry genes, the role of cilia and the nodal flow. We debate whether flow-sensing is based on morphogens or involves mechanosensing and explore mechanisms involved in asymmetric morphogenesis of the heart, including the NODAL-PITX2 cassette, intrinsic cellular chirality, and cardiac neural crest cells. Finally, we discuss environmental factors affecting LR axis formation and the potential development of therapeutics.

Summary

Understanding the genetic underpinnings of LR axis development and its effects on CHD is crucial for risk stratification of patients, leading to more effective treatment.