Craniosynostosis is the pathologic fusion of calvarial bones that is associated with abnormal skull growth and increased intracranial pressure. While the pathogenesis of single-suture craniosynostosis (which occurs in approximately 1/2500 live births) is poorly understood, genetic causes are likely given a 7–10% recurrence rate 
. However, recurrence rates based on pre-molecular epidemiological data may be upwardly biased because of contamination of nonsyndromic cases with individuals with single gene disorders. The most common form of craniosynostosis involves the fusion of a single suture (85–95%), but cases involving multiple sutures are relatively common (5–15%) 
. Approximately half of all single-suture craniosynostosis cases involve premature fusion of the sagittal suture, whereas premature fusion of the coronal and metopic sutures occurs in approximately 22% and 15% of cases, respectively. Lambdoid craniosynostosis is very rare, occurring in approximately 2% of all cases 
Craniosynostosis can be further categorized into syndromic and non-syndromic forms. Mutations in a number of different genes have been associated with syndromic craniosynostosis such as FGFR1-3, TWIST1, EFNB1, FBN1, MSX2, RAB23, RECQL4,
and TGFBR1-2 
. In fact, there are over one hundred well-established syndromic forms of craniosynostosis with known modes of inheritance, suggesting that genomic disposition plays an important role in this disease 
. While multiple reports have identified single gene mutations in nonsyndromic coronal synostosis 
, in general, mutations associated with single-suture synostosis remain elusive and rarely overlap with those causing syndromic forms of the disease 
. While this evidence suggests a strong genetic component exists for all forms of craniosynostosis, contributions from both genetic and environmental factors likely play a role in premature suture closure for non-syndromic forms of the disease. Results from a number of risk association studies aimed at identifying environmental risk factors related to craniosynostosis have been largely inconclusive 
; however, evidence for intrauterine head constraint 
, maternal smoking 
, and fertility treatments 
as predisposing causes does exist.
The fact that a number of environmental and genetic risk factors have been associated with developing craniosynostosis suggests that there is no single gene, factor, or pathway responsible for causing single-suture craniosynostosis. Rather, several independent mechanisms likely lead to the occurrence of several different forms of craniosynostosis, thus complicating the elucidation of these mechanisms 
. Numerous transcriptomic studies have been performed to gain insight into the pathogenesis of craniosynostosis, however the vast majority analyzed cases of syndromic synostosis 
, or a combination of syndromic and nonsyndromic cases 
. While these studies have provided great insight into the molecular mechanisms controlling the premature fusion of calvarial sutures in syndromic craniosynostosis, more work is needed to assess gene expression changes in nonsyndromic forms of this disease.
The transcriptomic study presented here is the largest of its kind, and the first to analyze gene expression changes in calvaria osteoblasts as they relate solely to nonsyndromic craniosynostosis. A rich set of transcriptomic data from a panel of well-characterized clinical samples was generated (199 synostosis cases and 50 controls), from which potentially pathogenic changes in gene expression among different forms of single-suture craniosynostosis were identified. In addition, subsequent pathway analysis on the dataset suggested that transcriptomic regulation of genes associated with extracellular matrix (ECM)-mediated focal adhesion play an important role in differentiating patients with craniosynostosis from unaffected individuals.