Background

Orofacial clefts (OFCs)—including cleft lip and cleft palate—comprise a significant portion of human structural birth defects and occur in approximately 1 in 700 children worldwide. Most OFCs are isolated, non-syndromic anomalies and have complex etiology caused by both genetic factors and environmental exposures. These disorders can have significant comorbidities and often require numerous surgical, dental, speech, nutritional, and behavioral interventions throughout life. As such, they impose a significant personal and economic burden on families, and also represent a significant public health challenge. Our interest is in understanding the genetic architecture of OFCs.

GCP- Genetics of Orofacial Cleft Project

The GCP began enrolling in March 2019, under the direction of Dr. Elizabeth Leslie, Assistant Professor of Human Genetics and Principal Investigator of the Leslie Lab at Emory University. The project oversees the identification of genes and gene/environment factors involved in birth defects of the head and face, and builds on previous research as well as data obtained from new participants recruited over the course of the study enrollment period. Specific disorders addressed in this project are non-syndromic orofacial clefts (i.e., cleft lip and/or palate not connected to a diagnosis of a known syndrome), syndromic forms of orofacial clefts, and other related disorders. A combination of statistical techniques coupled with molecular biology and genetic tools will allow us to identify genetic variants that may contribute to cleft formation.

Research goals

The Genetics of Orofacial Cleft Project is dedicated to understanding the different factors that contribute to craniofacial differences, including orofacial clefting. A lot is yet to be learned about the processes that give rise to these disorders, but previous studies point to personal genetic factors such as family history of clefting, other medical conditions, and environmental factors like exposure to certain substances during pregnancy. The overall goal of the study is to develop a better understanding of genes related to orofacial clefts and how they interact with the environment, in order to improve treatment, management, and prevention of orofacial clefts.

The immediate and direct contributions of our research are to genetic counseling and management of care for affected individuals. In addition, our findings are a resource for studies in mouse and other animal models that provide insight into the basic biology of development of these birth defects.

Recruitment

Although OFCs are among the most common structural birth defects and occur across all regions and demographic groups, research to date has mostly been limited to participants receiving treatment or residing near academic institutions and medical centers engaged in research of OFCs. By designing our study to accommodate remote participants and by using online recruitment strategies, we seek to expand availability and accessibility of research to geographically diverse populations.

Since 2019, through primarily social-media based recruitment, we have enrolled over 400 families into our study, and have now collected over 600 samples from OFC-affected individuals and their family members, and are well on our way to obtaining the numbers needed to perform genetic analyses.

Our project currently includes families from 43 out of 50 US states, as highlighted on the map below. Not pictured here are the countries involved internationally in this study, which include: Canada, France, Ireland, Germany, Australia, New Zealand, and the UK.

The responsiveness and commitment by our participating families demonstrates the potential of large-scale remote recruitment as a way to reach people who are interested in participating in research but would otherwise not have had the opportunity to volunteer. It also demonstrates that there is a need for more information than is currently available to families and individuals with OFCs.