Umar Muhammad, Tong Liping, Jin Hongting, Terebessy Tamas, Chen Di
Research Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong 518107, China.
Genes Dis. 2025 May 17;12(6):101690. doi: 10.1016/j.gendis.2025.101690. eCollection 2025 Nov.
Clubfoot, medically termed congenital talipes equinovarus (CTEV), is a prevalent musculoskeletal birth defect, affecting approximately 0.3% of all live births. This serious congenital anomaly results from structural abnormalities in the foot and lower leg, leading to abnormal positioning of the ankle and foot joints. This review provides a comprehensive overview of the causative factors associated with CTEV and evaluates current therapeutic approaches. Although variations in genes encoding contractile proteins of skeletal myofibers have been proposed as contributors to the etiology of CTEV, no definitive candidate genes have been conclusively linked to increased risk. However, genes such as , , and members of the , and clusters, as well as , have been implicated in the condition's development, playing critical roles in limb development, muscle formation, and tissue differentiation. Also, Axin1 plays a key role in joint formation and skeletal development by inhibiting β-catenin-BMP signaling. It could significantly serve as a therapeutic target for fibular hemimelia and multiple synostoses syndrome. The exact mechanisms and the extent of their physical and genetic interactions remain subjects of ongoing research. Understanding the genetic determinants and cellular pathways involved in CTEV is crucial for unravelling the pathophysiology of this complex deformity.
马蹄内翻足，医学上称为先天性马蹄内翻足（CTEV），是一种常见的肌肉骨骼先天性缺陷，约占所有活产婴儿的0.3%。这种严重的先天性畸形是由足部和小腿的结构异常引起的，导致踝关节和足部关节位置异常。本综述全面概述了与CTEV相关的致病因素，并评估了当前的治疗方法。虽然有人提出编码骨骼肌纤维收缩蛋白的基因变异是CTEV病因的一个因素，但尚未确定有明确的候选基因与风险增加有确凿联系。然而，诸如 、 以及 、 和 基因簇的成员，还有 等基因，都与该病的发展有关，在肢体发育、肌肉形成和组织分化中发挥着关键作用。此外，Axin1通过抑制β-连环蛋白-BMP信号通路在关节形成和骨骼发育中起关键作用。它可作为腓骨半肢畸形和多发性骨融合综合征的重要治疗靶点。其确切机制以及它们在物理和遗传相互作用方面的程度仍是正在进行研究的课题。了解CTEV中涉及的遗传决定因素和细胞途径对于阐明这种复杂畸形的病理生理学至关重要。
