First Trimester Fetal Clubfoot: A Novel Presentation of Severe Osteogenesis Imperfecta

Am J Med Genet A. 2025 Feb;197(2):e63867. doi: 10.1002/ajmg.a.63867. Epub 2024 Sep 13.

Abstract

Talipes equinovarus, also called clubfoot, is a relatively common congenital defect affecting approximately one in every 1000 live births. Most cases of clubfoot are expected to be idiopathic and unrelated to an underlying genetic syndrome. In approximately 20% of cases, a clear genetic etiology is identified. Here we present two cases of bilateral clubfoot identified via fetal ultrasound in the first trimester associated with osteogenesis imperfecta diagnosed in the second trimester. Both fetuses presented with multiple fractures and were identified to have loss-of-function variants in COL1A1. An association between clubfeet in the first trimester and osteogenesis imperfecta has not been previously reported to the best of our knowledge, which leads to unique opportunities for prompt diagnosis, genetic counseling and testing, and appropriate management.

Keywords: COL1A1; clubfoot; fetal fractures; first trimester ultrasound; osteogenesis imperfecta; skeletal dysplasia; talipes equinovarus.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Clubfoot* / diagnosis
  • Clubfoot* / diagnostic imaging
  • Clubfoot* / genetics
  • Clubfoot* / pathology
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Female
  • Fetus / diagnostic imaging
  • Fetus / pathology
  • Humans
  • Osteogenesis Imperfecta* / diagnosis
  • Osteogenesis Imperfecta* / diagnostic imaging
  • Osteogenesis Imperfecta* / genetics
  • Osteogenesis Imperfecta* / pathology
  • Pregnancy
  • Pregnancy Trimester, First*
  • Ultrasonography, Prenatal*

Substances

  • Collagen Type I, alpha 1 Chain
  • Collagen Type I