Genetics, epidemiology and management of clubfoot and related disorders
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 ankl...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225001795 |
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| author | Muhammad Umar Liping Tong Hongting Jin Tamas Terebessy Di Chen |
| author_facet | Muhammad Umar Liping Tong Hongting Jin Tamas Terebessy Di Chen |
| author_sort | Muhammad Umar |
| collection | DOAJ |
| description | 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 TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, 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. |
| format | Article |
| id | doaj-art-e285fb089652483787e714158aec9c85 |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-e285fb089652483787e714158aec9c852025-08-24T05:13:20ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610169010.1016/j.gendis.2025.101690Genetics, epidemiology and management of clubfoot and related disordersMuhammad Umar0Liping Tong1Hongting Jin2Tamas Terebessy3Di Chen4Research 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, ChinaResearch Center for Computer-aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical University and Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, Zhejiang 310053, China; Corresponding author.Centre for Translational Medicine, Department of Orthopaedics, Semmelweis University, Üllői út 26, Budapest 1085, Hungary; Translational European-Asian Network (TEA-NET), Partner of Translational Medicine Working Group, Academia Europaea (AE), Üllői út 26, Budapest 1085, Hungary; Corresponding author. Centre for Translational Medicine, Department of Orthopaedics, Semmelweis University, Üllői út 26, Budapest 1085, Hungary.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; Translational European-Asian Network (TEA-NET), Partner of Translational Medicine Working Group, Academia Europaea (AE), Üllői út 26, Budapest 1085, Hungary; Corresponding author. Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong 518000, China.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 TBX4, PITX1, and members of the HOXA, HOXC, and HOXD clusters, as well as NAT2, 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.http://www.sciencedirect.com/science/article/pii/S2352304225001795Associated genes pathwaysCongenital anomalyCongenitaltalipes equinovarusEtiology of CTEVFoot deformity |
| spellingShingle | Muhammad Umar Liping Tong Hongting Jin Tamas Terebessy Di Chen Genetics, epidemiology and management of clubfoot and related disorders Genes and Diseases Associated genes pathways Congenital anomaly Congenitaltalipes equinovarus Etiology of CTEV Foot deformity |
| title | Genetics, epidemiology and management of clubfoot and related disorders |
| title_full | Genetics, epidemiology and management of clubfoot and related disorders |
| title_fullStr | Genetics, epidemiology and management of clubfoot and related disorders |
| title_full_unstemmed | Genetics, epidemiology and management of clubfoot and related disorders |
| title_short | Genetics, epidemiology and management of clubfoot and related disorders |
| title_sort | genetics epidemiology and management of clubfoot and related disorders |
| topic | Associated genes pathways Congenital anomaly Congenitaltalipes equinovarus Etiology of CTEV Foot deformity |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225001795 |
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