He Yukun, Verleyen Marlies, Callewaert Bert, Burssens Arne, Audenaert Emmanuel
Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Orthopedic Surgery and Traumatology, Ghent University Hospital, Ghent, Belgium.
Clin Genet. 2025 May;107(5):485-494. doi: 10.1111/cge.14730. Epub 2025 Feb 18.
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.
足弓形态的变异，包括扁平足（平足症）和高弓足（高弓足畸形），范围从无症状到使人衰弱。关于足弓几何形状的遗传学研究有限。本系统综述旨在确定与足弓形态相关的单核苷酸多态性（SNP）。该综述方案已在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42024537877）登记。检索了PubMed、考克兰图书馆、Embase和科学网，查找截至2023年12月发表的与足弓形态相关的SNP研究。19项符合条件的研究（2006 - 2020年）在影响结缔组织的疾病（12项研究，如马凡综合征）、神经疾病（6项研究，如夏科 - 马里 - 图斯病）和肌肉疾病（1项研究，如远端关节弯曲综合征）中鉴定出137个SNP。虽然没有研究直接将SNP与足弓形态联系起来，但有三项研究探讨了与足弓变异相关的遗传疾病中的SNP。扁平足与结缔组织疾病有关，高弓足与神经病变和肌肉病变有关。仅发现两个重复的SNP。本综述未发现直接研究影响足弓形态的SNP，凸显了一个重大的研究空白。未来的研究应在更大的队列中检查SNP，以区分自然变异和病理驱动的畸形。为提高可重复性，应开发标准化方法和统一的遗传数据库（包括常见性状的表型数据）。
