A systematic review of association studies of common variants associated with idiopathic congenital talipes equinovarus (ICTEV) in humans in the past 30 years

The genetic cause of idiopathic congenital talipes equinovarus (ICTEV) is largely unknown. We performed a systematic review to describe the findings from 21 studies that have examined the genetic variants related to ICTEV, and to evaluate the quality of reporting. We found that ICTEV was positively associated with Hox family genes, collagen family genes, GLI3, N-acetylation genes, T-box family genes, apoptotic pathway genes, and muscle contractile family genes. Negative and controversial results were also discussed, and several genes associated with ICTEV were identified. Due to the limitation of the included studies, rare coding variants should be further investigated, sample size should be enlarged, and candidate genes should be replicated in larger ICTEV populations. Epigenetic study, pathways, chromosome capture, and detailed gene-environment interaction will also allow further elucidation of factors involved in ICTEV pathogenesis and may shed light on diagnosis and timely and accurate interventions.