Unraveling the Genetic Landscape of Foot Arch Morphology: A Systematic Review of Single Nucleotide Polymorphisms

Abstract

Variations in foot arch morphology, including flat feet (pes planus) and high arches (pes cavus), range from asymptomatic to debilitating. Limited research exists on the genetics of foot arch geometry. This systematic review aims to identify single nucleotide polymorphisms (SNPs) linked to foot arch morphology. The review protocol was registered in PROSPERO (CRD42024537877). PubMed, The Cochrane Library, Embase, and Web of Science were searched for studies on SNPs related to foot arch morphology published up to December 2023. Nineteen eligible studies (2006–2020) identified 137 SNPs across conditions affecting connective tissue (12 studies, e.g., Marfan Syndrome), nerves (six studies, e.g., Charcot–Marie–Tooth Disease), and muscles (one study, e.g., Distal Arthrogryposis Syndromes). While no studies directly linked SNPs to foot arch morphology, three explored SNPs in genetic diseases associated with foot arch variations. Pes planus was linked to connective tissue disorders, and pes cavus to neuropathies and myopathies. Only two replicated SNPs were found. This review found no direct studies of SNPs influencing foot arch morphology, highlighting a significant research gap. Future research should examine SNPs in larger cohorts to differentiate natural variations from pathology-driven deformities. To enhance reproducibility, standardized methodologies, and a unified genetic database (including phenotypic data on common traits) should be developed.