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Study Description

Isolated clubfoot or idiopathic talipes equinovarus (ITEV) is one of the five most common birth defects, affecting approximately 4,000 newborns each year in the US. While the orthopedic care of these children has improved, long-term problems persist and the health care costs are significant. Studies suggest that clubfoot is a complex disorder with segregation analyses and family studies indicating that genetic factors play an important etiologic role in the development of clubfoot. Only one environmental factor, maternal smoking during pregnancy, has been implicated. We postulate that a small number of genes account for a substantial fraction of clubfoot and that these genes can be identified in a defined population. The challenge now is to identify the genetic loci and, later, the effect of environmental exposures. To accomplish this task, it is important to have a well-defined population and the methodology to detect linkage with and without association. Towards these goals, we have identified and characterized multiplex clubfoot families, including two large clubfoot families, a resource which is among the largest ITEV populations in existence. We will perform a high-density SNP genome scan (GWAS) on our clubfoot dataset to identify chromosomal regions that may harbor clubfoot genes with subsequent interrogation of these regions and candidate genes. We are in a position with our unique clubfoot population and with the methodology in place to undertake this study. The study phases are: 1) continued ascertainment of multiplex and simplex families and 2) GWAS and characterization of identified chromosomal regions and candidate genes. The results of this study will provide data essential to the identification of the gene(s) contributing to the clubfoot phenotype. Identification of high-risk genotypes can lead to the development of prevention programs in selected populations and may suggest gene-based prevention strategies.

  • Study Weblink: Clubfoot
  • Study Types: Multiplex Families, Parent-Offspring Trios
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 1903

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Multiplex and simplex (trio) clubfoot families.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanOmniExpress-12v1.0 731442 N/A
Study History

This family-based isolated clubfoot gene discovery study has been ongoing since 1992. Probands and there families are ascertained in various orthopedic centers and enrolled in the study. The dataset is composed of both non-Hispanic white and Hispanic (Mexican) populations. Information about prenatal exposures, including smoking, alcohol, vitamin and specific pregnancy complications are collected from the mothers of all affected individuals.

Selected publications
Diseases/Traits Related to Study (MESH terms)
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Study Attribution