The etiology of idiopathic congenital talipes equinovarus: a systematic review

Abstract

BackgroundAlso known as clubfoot, idiopathic congenital talipes equinovarus (ICTEV) is the most common pediatric deformity and occurs in 1 in every 1000 live births. Even though it has been widely researched, the etiology of ICTEV remains poorly understood and is often described as being based on a multifactorial genesis. Genetic and environmental factors seem to have a major role in the development of this disease. Thus, the aim of this review is to analyze the available literature to document the current evidence on ICTEV etiology.MethodsThe literature on ICTEV etiology was systematically reviewed using the following inclusion criteria: studies of any level of evidence, reporting clinical or preclinical results, published in the last 20 years (1998–2018), and dealing with the etiology of ICTEV.ResultsA total of 48 articles were included. ICTEV etiology is still controversial. Several hypotheses have been researched, but none of them are decisive. Emerging evidence suggests a role of several pathways and gene families associated with limb development (HOX family; PITX1-TBX4), the apoptotic pathway (caspases), and muscle contractile protein (troponin and tropomyosin), but a major candidate gene has still not been identified. Strong recent evidence emerging from twin studies confirmed major roles of genetics and the environment in the disease pathogenesis.ConclusionsThe available literature on the etiology of ICTEV presents major limitations in terms of great heterogeneity and a lack of high-profile studies. Although many studies focus on the genetic background of the disease, there is lack of consensus on one or multiple targets. Genetics and smoking seem to be strongly associated with ICTEV etiology, but more studies are needed to understand the complex and multifactorial genesis of this common congenital lower-limb disease.

Congenital clubfoot in Europe: A population‐based study

“…It has higher recurrence within families; however, a twin study suggested that environmental factors also play a significant role in the etiology of congenital clubfoot (Engell et al, ). Several environmental risk factors, in particular maternal smoking, have been related to the risk of congenital clubfoot (Pavone et al, ; Werler et al, ). Some maternal medical conditions and medication use could increase the risk of congenital clubfoot, such as obesity (Werler et al, ) and use of selective serotonin reuptake inhibitors (SSRI) (Wemakor et al, ; Yazdy, Mitchell, Louik, & Werler, ).…”

Novel contribution to clubfoot pathogenesis: The possible role of extracellular matrix proteins

“…Idiopathic pes equinovarus (clubfoot) belongs to a group of fibroproliferative disorders involving the musculoskeletal system and its origin remains unknown. This defect occurs approximately once per 1000 births . The guideline on the diagnosis and treatment of this disease was recently published by Besselaar et al These methods, although successful, are of a long‐term nature and very demanding for the child patients and their parents alike because a number of plasters need to be applied starting at a very young age.…”

Orthopedic findings in arthrogryposis and congenital Zika syndrome: A case series

“…However, in 80% of cases, this occurs separately or as an idiopathy. Genetic and environmental components are believed to be involved (Gibbons & Gray, 2013;Pavone et al, 2018).…”