Kids First: Whole Genome Sequencing of Nonsyndromic Craniosynostosis

The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Nonsyndromic craniosynostosis (NCS) is a common, major structural birth defect - due to the premature fusion of one or more cranial sutures - that requires extensive surgical correction and is associated with considerable ongoing medical problems and health care costs. Because little is known about the causes of NCS, whole genome sequencing will help advance knowledge of genetic factors contributing to the etiology of NCS. Data from this project will lead to a better understanding of biological processes involved in the etiology of NCS and provide critical insights for development of early diagnostic tools and therapeutic strategies. ]]> Inclusion Criteria: Presence of craniosynostosis confirmed by head CT, surgical reports, and/or clinical genetics evaluation. Exclusion Criteria: Identification of single gene recognizable craniosynostosis syndrome with known etiology (i.e. Apert syndrome, Crouzon syndrome)]]> Craniosynostosis (CS), the premature fusion of one or more cranial sutures, is a common defect occurring in 1 in 2,500 live births. About 85% of infants with CS present as nonsyndromic (i.e., without unrelated, major birth defects or developmental delay). Nonsyndromic CS (NCS) is a heterogeneous condition with presumed multifactorial etiology; however, its causes remain largely unknown. As such, primary prevention strategies for this defect are limited. In order to understand the etiology of this common birth defect, multiple investigators with special expertise and interests in craniosynostosis, led by Dr. Simeon Boyadjiev Boyd, formed the International Craniosynostosis Consortium (ICC; https://myhs.ucdmc.ucdavis.edu/web/dr.-boyd-s-lab) to create a clinical database and sample repository of well-characterized families with NCS. The ICC has recruited large numbers of NCS case families and controls over the course of many years of domestic and international collaborative studies. For the current Kids First project, whole genome sequencing (WGS) will be performed in 300 case-parent trios and in multiplex families with NCS. ]]>