Human Genetics Unit, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo, Sri Lanka.
Orphanet J Rare Dis. 2022 May 12;17(1):198. doi: 10.1186/s13023-022-02339-0.
The formation of the digits is a tightly regulated process. During embryogenesis, disturbance of genetic pathways in limb development could result in syndactyly; a common congenital malformation consisting of webbing in adjacent digits. Currently, there is a paucity of knowledge regarding the exact developmental mechanism leading to this condition. The best studied canonical interactions of Wingless-type-Bone Morphogenic Protein-Fibroblast Growth Factor (WNT-BMP-FGF8), plays a role in the interdigital cell death (ICD) which is thought to be repressed in human syndactyly. Animal studies have displayed other pathways such as the Notch signaling, metalloprotease and non-canonical WNT-Planar cell polarity (PCP), to also contribute to failure of ICD, although less prominence has been given. The current diagnosis is based on a clinical evaluation followed by radiography when indicated, and surgical release of digits at 6 months of age is recommended. This review discusses the interactions repressing ICD in syndactyly, and characterizes genes associated with non-syndromic and selected syndromes involving syndactyly, according to the best studied canonical WNT-BMP-FGF interactions in humans. Additionally, the controversies regarding the current syndactyly classification and the effect of non-coding elements are evaluated, which to our knowledge has not been previously highlighted. The aim of the review is to better understand the developmental process leading to this condition.
指（趾）的形成是一个受到严格调控的过程。在胚胎发育过程中，肢体发育过程中遗传途径的干扰可能导致并指；一种常见的先天性畸形，由相邻指（趾）的蹼状连接组成。目前，对于导致这种情况的确切发育机制知之甚少。研究最多的经典 Wingless 型-Bone Morphogenic Protein-Fibroblast Growth Factor（WNT-BMP-FGF8）相互作用，在指间细胞死亡（ICD）中起作用，据认为 ICD 在人类并指中受到抑制。动物研究显示其他途径，如 Notch 信号转导、金属蛋白酶和非经典 WNT-Planar cell polarity（PCP），也有助于 ICD 失败，尽管关注较少。目前的诊断基于临床评估，然后在需要时进行放射学检查，并建议在 6 个月大时进行手指释放手术。这篇综述讨论了在并指中抑制 ICD 的相互作用，并根据人类研究最多的经典 WNT-BMP-FGF 相互作用，描述了与非综合征和涉及并指的选定综合征相关的基因。此外，还评估了当前并指分类的争议和非编码元件的影响，据我们所知，这尚未得到强调。综述的目的是更好地了解导致这种情况的发育过程。
