Each year, approximately 200,000 children (about one in 700 live births) are born with cleft lip and palate (CLP). Worldwide, a child with CLP is born every three minutes. In the U.S., approximately 16 children are born with CLP each day – making it three times more common than all childhood cancers combined.

Children with CLP have considerable difficulty eating, drinking and breathing because their nasal and oral airways are not separated. They typically require multiple corrective and cosmetic surgeries – sometimes a dozen or more. They may also need major orthodontic work and speech therapy into their teenage years. In the U.S., the total cost of health care for CLP is estimated at around $150,000 per child, which translates to an annual cost of approximately $850 million. Many patients in the developing world do not have access to – or can’t afford – medical treatment and will live with increased health risks and the social stigma associated with ‘looking different’.

Imagine a world where we could predict an individual’s CLP risk before they’re conceived and intervene with simple dietary modifications to prevent the disorder. The Cox Lab’s research program is aimed at moving closer to this reality and sparing children worldwide from CLP and other common craniofacial conditions.

Working to prevent or minimize facial birth defects

Talented surgeons and clinical teams, like at Seattle Children’s Craniofacial Center, do a phenomenal job treating and managing the complex medical care needed by patients with facial birth defects. A major complicating factor in delivering effective treatments is that patients’ clinical presentation can vary markedly - from minor to severe, depending on the individual. This variability makes it difficult to predict surgery outcomes and confounds counseling regarding a woman’s risk of having future children with craniofacial anomalies. It also can limit clinicians’ ability to accurately diagnose patients.

Polarized epithelial cells showing the localization of ZO1 protein (red) at the sites of adhesion. 
Nuclear DNA is blue.Polarized epithelial cells showing the localization of ZO1 protein (red) at the sites of adhesion. Nuclear DNA is blue.

Over the last few decades, researchers have begun to identify genetic factors that put a child at risk of being born with a facial anomaly. Yet these factors explain only a small percentage of the contributions to these conditions and there is still a relatively poor understanding of how each factor perturbs normal facial development. We need to better understand these mechanisms if we are to improve treatment outcomes, reduce the severity of the condition or develop preventative therapies. Our goal is to reduce the burden of medical treatment on children, and the cost and emotional toll on families.

The Cox Lab’s team conducts basic research to identify and understand how different genetic, nutritional and environmental factors determine whether a child will be born with a facial birth defect and how severe that malformation will be. While the principal focus of the lab is on cleft lip and palate, we also have research projects directed at two other common facial birth defects: midface hypoplasia and craniofacial microsomia. These conditions can be equally challenging to treat in the clinic and for which even less is known about the causative factors.

Investigator Biography

Dr. Timothy Cox

Timothy C. Cox, PhD, is a professor in the Department of Pediatrics’ Division of Craniofacial Medicine at the University of Washington School of Medicine, and inaugural holder of the Laurel Endowed Chair in Pediatric Craniofacial Research. Cox is a member of Seattle Children’s Research Institute’s Center for Developmental Biology and Regenerative Medicine and an affiliate member of the University of Washington’s Center on Human Development and Disability. He also holds an adjunct faculty appointment in the Department of Anatomy and Developmental Biology at Monash University (Australia).

Prior to joining Seattle Children’s Research Institute, he held several leading positions in craniofacial medicine in Australia, including director of genetic programs at the Australian Craniofacial Unit and co-director of Monash University’s MouseWorks, a highly regarded mouse genetic modification facility. Cox is also a past president of the Australia and New Zealand Society for Cell and Developmental Biology.

Research Funding

This research is only possible through targeted research grants and philanthropic support from varied sources. Recent and current funding for our work has been provided by:

  • The National Institute of Dental and Craniofacial Research (NIDCR) at NIH
  • The National Institute of Child Health and Development (NICHD) at NIH
  • The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at NIH
  • The Laurel Foundation
  • The Murdock Charitable Trust
  • The Cleft Palate Foundation
  • The Jorge Posada Foundation
  • The Canadian Institutes of Health Research
  • The National Health & Medical Research Council of Australia
  • Seattle Children’s Research Institute