Isolated congenital vertical talus: Genetics and genomics

Abstract

Congenital vertical talus (CVT) is a distinct orthopedic condition where the bone structure and number are normal in the affected foot, but the orientation of the bones is not correct. The abnormal orientation of the bones in the affected foot is believed to be due to muscle imbalance. There are a shortening and dorsal displacement of the peroneal tendons and tibialis posterior tendon, resulting in the clinical appearance of a severe rigid flatfoot. The underlying etiology of the CVT is unknown, and limited studies have been performed to decipher the genetics of CVT. The purpose of this review is to highlight the key research articles within the CVT genetics and genomics fields that were published previously. Herein, we reviewed the current literature and discussed the genetic studies carried out in families and patients with an isolated form of CVT. It is believed that CVT segregates in an autosomal dominant fashion. Most of the studies used a candidate gene approach to identify CVT causative variants. Variants in growth differentiation factor 5, HOXD10, teashirt zinc finger homeobox 1, and skeletal muscle contractile genes have been associated with CVT. An unbiased and hypothesis-free approach of whole-exome sequencing is much needed to unwire the genetic network underlying distal hind limb development and to improve our understanding of the gene regulatory mechanism in this musculoskeletal disorder. Moreover, this review focuses on highlighting the importance of the identification of the genetics of CVT and its implications in early clinical diagnosis and management of patients.