Basic Science Research
In addition to clinical studies, members of the Center for Craniofacial Research are also dedicated to understanding craniofacial disorders at the cellular and molecular level.
This basic science research is a collaboration between Seattle Children's and the University of Washington.
As understanding increases at the molecular level, the center will be able use this knowledge to design new treatments for conditions seen in the craniofacial clinic.
Craniosynostosis Research Program
Isolated craniosynostosis (premature fusion of the skull bones) occurs in approximately 1 out of 2,500 births. The sutures of the skull are specialized joints between skull bones that expand during normal brain growth.
Diagram by Raymond Sze. Figure 1. The sutures of the skull are specialized joints between skull bones that expand during normal brain growth.
Premature suture fusion results in abnormalities in head shape due to restriction of growth in the region of a fused suture.
These changes of head shape can be associated with increased pressure within the skull that can result in permanent brain injury.
In addition to the risks of brain injury, craniosynostosis is often associated with alteration of craniofacial growth leading to midfacial hypoplasia, dental malocclusion and orbital deformation.
The combination of craniosynostosis and its associated facial malformations leads to significant health problems.
Dr. Michael Cunningham, Dr. Richard Hopper, research scientist Marianne Seto and their lab group use bone cell lines and animal models to study the molecular and developmental causes of craniosynostosis.
Their research is focused on causes of several hereditary craniosynostosis syndromes, including Apert, Crouzon, Saethre-Chotzen and Muenke.
In addition to these relatively rare forms of craniosynostosis, the Cunningham Lab investigates the molecular and developmental causes of isolated single-suture craniosynostosis.
Through the use of modern techniques of molecular biology, mutational analysis, expression analysis and cell biology, the Cunningham Lab investigates the normal development of the human skull and biologic causes (pathogenesis) of craniosynostosis as a way to identify alternative diagnostic, treatment and prevention strategies.
Craniofacial Genetics
Dr. Anne V. Hing studies the genetic causes of craniofacial conditions. She recently studied four related Native Alaskans from a geographically isolated community with birth defects involving the bones of the face.
Figure 2. Three-dimensional CT scans of a normal infant (left) and a child with right coronal synostosis (right). The scans demonstrate the secondary changes in skull growth associated with craniosynostosis. Note: Sutures were darkened digitally for demonstration purposes.
Their facial features include lower eyelid coloboma (a notch in the eyelid), choanal atresia (bony obstruction of the nasal airway), orofacial clefting (a cleft extending from the mouth into the upper parts of the face), midface hypoplasia and external ear malformation with hearing loss.
Cranial imaging studies demonstrate a unique abnormality in the cheekbones. Dr. Hing's team proposes that these children have inherited a rare autosomal recessive oculo-oto-facial dysplasia (OOFD) that has never been described before. It's possible that they have inherited two copies of the same gene mutation from a common ancestor.
Initial estimates suggest that the carrier frequency in this Native Alaskan population may be as high as 1 in 29. This condition has significant infant morbidity and mortality secondary to choanal atresia, which causes breathing obstruction and requires emergency airway management.
Also, these children have developed profound progressive hearing loss and have required multiple corrective craniofacial surgeries throughout childhood and adulthood.
These complications and the inability of prenatal ultrasound to predict choanal atresia confirm the importance of developing carrier testing for this population. Identification of the genetic cause will facilitate identification of gene carriers within the population.
The long-term goal of this project is to determine the molecular basis of OOFD. This will be achieved by identifying the genetic cause using homozygosity mapping and determination of the specific gene mutation in affected individuals.
Such studies could ultimately lead to the development of a genetic screening test and would increase our understanding of craniofacial development.
Facial Feature Differences in 22q11.2 Deletion Syndrome
Dr. Carrie Heike is a pediatrician who is receiving her fellowship training in the Craniofacial Center. She is currently conducting a study to learn more about children with 22q11.2 deletion syndrome (also known as velocardiofacial syndrome).
22q11.2 deletion syndrome is a genetic condition that is thought to affect 1 in 4,000 newborns.
Although 90% of individuals with 22q11.2 deletion syndrome have a large deletion of genetic material on chromosome 22, the associated characteristics vary widely. These can include certain facial features, congenital heart disease, cleft palate and psychiatric disorders.
The primary aim of this study is to identify differences in facial features of children with 22q11.2 deletion syndrome using facial measurements taken on three-dimensional photographs.
Dr. Heike is also looking at single nucleotide polymorphisms (single base-pair changes) in the non-deleted chromosome 22.
The purpose of this part of the study is to determine if these genetic changes are associated with the wide range of clinical features observed in children with the 22q11.2 deletion.