Craniosynostosis is a relatively common birth defect characterized by the 
premature fusion of one or more cranial sutures. Examples of craniosynostosis 
syndromes include Crouzon (CS), Pfeiffer (PS), and Apert (AS) syndrome, with 
clinical characteristics such as midface hypoplasia, hypertelorism, and in some 
cases, limb defects. Mutations in Fibroblast Growth Factor Receptor-2 comprise 
the majority of known mutations in syndromic forms of craniosynostosis. A number 
of clinical reports of FGFR-associated craniosynostosis patients and mouse 
mutants have been linked to gastrointestinal tract (GIT) disorders, leading to 
the hypothesis of a direct link between FGFR-associated craniosynostosis 
syndromes and GIT malformations. We conducted an investigation to determine GIT 
symptoms in a sample of FGFR-associated craniosynostosis syndrome patients and a 
mouse model of CS containing a mutation (W290R) in Fgfr2. We found that, 
compared to the general population, the incidence of intestinal/bowel 
malrotation (IM) was present at a higher level in our sample population of 
patients with FGFR-associated craniosynostosis syndromes. We also showed that 
the mouse model of CS had an increased incidence of cecal displacement, 
suggestive of IM. These findings suggest a direct relationship between 
FGFR-related craniosynostosis syndromes and GIT malformations. Our study may 
shed further light on the potential widespread impact FGFR mutations on 
different developmental systems. Based on reports of GIT malformations in 
children with craniosynostosis syndromes and substantiation with our animal 
model, GIT malformations should be considered in any child with an 
FGFR2-associated craniosynostosis syndrome. © 2016 Wiley Periodicals, Inc.