Scholarlink

<p>Holoprosencephaly (HPE) is the most common structural anomaly of developing forebrain, characterized by incomplete separation of the cerebral hemispheres. While mutations in the Sonic Hedgehog (SHH) signaling pathway remain the most established genetic cause, recent studies have identified an expanding list of genes and molecular networks involved in the pathogenesis of HPE. These include modulators of the NODAL, NOTCH, WNT/PCP, FGF, and RAS/ERK1/2 pathways as well as components of ciliary structures and cohesin complexes. Incomplete penetrance, broad phenotypic heterogeneity, and gene-environment interactions complicate diagnostic and counselling efforts. This review summarizes recent insights into the molecular mechanisms of HPE, highlighting key signalling networks, gene candidates, and phenotypic correlations. We also discuss under-recognised contributors such as cohesin and ciliary gene defects, which may account for a significant subset of unresolved cases. Finally, we propose a diagnostic framework incorporating clinical stratification, extended gene panels, and consideration of syndromic features.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月17日

查看全文
  • Filip Glista,
  • Julia Nienartowicz,
  • Ewelina Bukowska-Olech

摘要

Holoprosencephaly (HPE) is the most common structural anomaly of developing forebrain, characterized by incomplete separation of the cerebral hemispheres. While mutations in the Sonic Hedgehog (SHH) signaling pathway remain the most established genetic cause, recent studies have identified an expanding list of genes and molecular networks involved in the pathogenesis of HPE. These include modulators of the NODAL, NOTCH, WNT/PCP, FGF, and RAS/ERK1/2 pathways as well as components of ciliary structures and cohesin complexes. Incomplete penetrance, broad phenotypic heterogeneity, and gene-environment interactions complicate diagnostic and counselling efforts. This review summarizes recent insights into the molecular mechanisms of HPE, highlighting key signalling networks, gene candidates, and phenotypic correlations. We also discuss under-recognised contributors such as cohesin and ciliary gene defects, which may account for a significant subset of unresolved cases. Finally, we propose a diagnostic framework incorporating clinical stratification, extended gene panels, and consideration of syndromic features.