CHOP Frontier Program Leveraging Genomics to Improve Craniofacial Treatment

The Craniofacial Program at CHOP is harnessing genomic technologies to improve diagnostics, predict treatment outcomes, and generate the world’s largest craniofacial biobank for patients like Grace Hewlett.

Improving clinical care and growing translational research for children with craniofacial anomalies is at the heart of the Craniofacial Program, newly designated as a 2025 Frontier Program at Children's Hospital of Philadelphia.

An expert team of CHOP scientists and surgeons are harnessing genomic technologies to improve diagnostics, predict treatment outcomes, and generate the world's largest craniofacial biobank for children with orofacial clefts, craniosynostosis, hemifacial microsomia, and fibrous dysplasia.

Craniofacial anomalies are among the most common human birth conditions, causing facial disfigurements, as well as dysfunctions in speech, feeding, and breathing. Symptoms can reemerge even following surgeries, and many families worldwide lack access to the kind of multidisciplinary team of medical specialists that is uniquely available at CHOP.

While CHOP's Craniofacial Program is one of the largest of its kind — with more than 1,200 admissions for surgical procedures each year — treatment for children with complex craniofacial conditions often requires multiple procedures over many years. The Craniofacial Program will be instrumental helping even more families while bringing new therapies to market.

"Right now, surgery is the only option we have available for these patients," said Eric Chien-Wei Liao, MD, PhD, a pediatric plastic surgeon-scientist and the Founding Director of the Center for Craniofacial Innovation at CHOP Research Institute.

Saylor Wilgus was born with craniosynostosis, which was surgically corrected at CHOP by Jesse Taylor, MD, who co-leads the Craniofacial Frontier Program.

Dr. Liao leads the Craniofacial Program alongside Jesse Taylor, MD, Chief of the Division of Plastic and Reconstructive Surgery, and William Peranteau, MD, an Associate Professor of Surgery. All three clinician-scientists bring years of expertise in fetal care, human genetics, and developmental biology research to the program.

For example, in the Liao Laboratory, 3-D live cell imaging of cleft formation in zebrafish models is helping Dr. Liao and colleagues understand the genetic basis of cleft palate.

"Being able to see the mouth form and open for the first time in an animal model is the Holy Grail of embryology," Dr. Liao said. "The same genes in humans that cause cleft lip, when we disrupt them in the zebrafish, they make clefts, and we can rescue them."

Expanding on that research, the Craniofacial Program team is collecting patient biospecimens and phenotypic data to build the world's largest craniofacial biobank. They will use machine learning to integrate genetic, imaging, and clinical data to identify the human gene variants associated with craniofacial malformations in various disorders. That information will then be input into a clinical-support dashboard to reveal important information for medical teams when making treatment decisions.

"Right now, when we take care of patients, we are biobanking and sequencing, but we don't know what that sequencing information means for the natural history of the disease of the child," Dr. Liao said. "We'll now have the phenotypic, omics, and patient-reported data to inform our research, and we can link that data with outcomes so that we can better care for patients."

The Craniofacial Program team also will use that information to develop and test a gene therapy to treat certain congenital craniofacial conditions. Their goal is to bring a new gene therapy to a clinical trial within the next three years.

"If we are successful," Dr. Liao said, "this and other projects will truly change care for large populations of children over time."