Journal Article

Genotype-phenotype correlation in clubfoot (talipes equinovarus)

Hordyjewska-Kowalczyk, Ewa, Jamsheer, Aleksander, Tylzanowski, Przemko, Nowosad, Karol

2022

Overview

Clubfoot (talipes equinovarus) is a congenital malformation affecting muscles, bones, connective tissue and vascular or neurological structures in limbs. It has a complex aetiology, both genetic and environmental. To date, the most important findings in clubfoot genetics involve PITX1 variants, which were linked to clubfoot phenotype in mice and humans. Additionally, copy number variations encompassing TBX4 or single nucleotide variants in HOXC11, the molecular targets of the PITX1 transcription factor, were linked to the clubfoot phenotype. In general, genes of cytoskeleton and muscle contractile apparatus, as well as components of the extracellular matrix and connective tissue, are frequently linked with clubfoot aetiology. Last but not least, an equally important element, that brings us closer to a better understanding of the clubfoot genotype/phenotype correlation, are studies on the two known animal models of clubfoot—the pma or EphA4 mice. This review will summarise the current state of knowledge of the molecular basis of this congenital malformation.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: and neonatal diseases and abnormalities / Animal models / Animals / Chromosomes / Classification / Clubfoot / Clubfoot - genetics / congenital / Congenital defects / Congenital diseases / Connective tissues / Copy number / Cytoskeleton / Defects / Disease / DNA Copy Number Variations / EphA4 protein / Etiology / Extracellular matrix / Foot diseases / Genes / Genetic Association Studies / genetic predisposition to disease / genetic research / Genotype & phenotype / Genotypes / hereditary / Hip dislocation / Homeodomain Proteins - genetics / human genetics / Humans / Hypotheses / Mice / Muscle contraction / Muscles / Mutation / Phenotype / Phenotypes / Review / Transcription Factors - genetics