Exploring the Genetic and Pathobiological Pathways of Talipes Equinovarus: a Short Narrative Review

Yasir Naseem Khan, Mohammad Imad A. Mustafa Mahmud

Abstract

Background: Talipes equinovarus (TEV), commonly referred to as clubfoot, is a prevalent congenital foot deformity characterized by a combination of osteochondral tissue anomalies including hindfoot varus (supination or inversion of the subtalar joint), forefoot adduction (metatarsus adductus), exaggerated midfoot arch (cavus), and restricted ankle dorsiflexion (equinus). The incidence of TEV ranges from 0.5 to 2.0 per 1000 live births, and its etiology is believed to involve a complex interplay of genetic and environmental factors. Despite its long-standing recognition, the precise cause of TEV remains largely unknown. Various genetic studies, including candidate gene association studies, copy number variation analyses, linkage analyses, whole-exome sequencing, and whole-genome sequencing, have identified the specific genes implicated in TEV pathogenesis. However, the existing literature remains insufficient to pinpoint the exact genetic causes of familial cases, as most investigations have concentrated on sporadic instances, leaving many speculative genetic factors. Methods: This narrative review synthesizes the existing literature on the environmental, molecular, and genetic factors contributing to TEV while elucidating the pathobiological mechanisms involved in its development. Results: Evidence suggests that TEV exhibit familial segregation patterns consistent with both autosomal dominant and recessive inheritance, as well as autosomal dominant inheritance with incomplete penetrance, underscoring the significant role of genetic components. Notably, the concordance rate for TEV was markedly higher in monozygotic twins (32%) than in dizygotic twins (2.9%), reinforcing the genetic underpinning of the condition. Conclusions: According to our review outcomes, TEV simultaneously originates from genetic predispositions and environmental influences that disrupt normal mitotic division of the cytoskeleton in the lower limbs. To advance our understanding of TEV, there is a pressing need for large-scale, multicenter collaborative studies employing advanced genetic techniques, such as genome-wide association studies (GWAS) with single nucleotide polymorphism scans and linkage analysis in extensive family cohorts.


Keywords: Talipes equinovarus, genetics, pathology


 

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