Gene expression profiling in human craniosynostoses: a tool to investigate the molecular basis of suture ossification

Non-syndromic craniosynostoses (NSC) occur as isolated skull malformations due to the premature ossification of one (single-suture forms) or more (complex forms) calvarial sutures and represent the most frequent form of craniosynostosis worldwide. The etiology of NSC is still largely unknown as a genetic basis can be rarely demonstrated especially in single-suture forms. In these cases, during the prenatal/perinatal development of affected patients, only one suture undergoes a premature direct ossification within an otherwise physiologically grown skull. This could suggest that definite somatic alterations, possibly due to unclear environmental agents, occur locally at the site of premature suture fusion during skull development. A promising tool to investigate the molecular mechanisms that may orchestrate this event is the comparative analysis of suture- and synostosis-derived tissues and cells.

This review focuses on the different studies that attempted to clarify this issue using genome-wide microarray-based technologies for the comparative analysis of gene expression profiles. All relevant results have been comprehensively reviewed, possibly compared, and critically discussed.

Due to the heterogeneity of the dataset available in the literature, a univocal CRS-associated molecular profile could not be deciphered. Most differentially expressed genes are found in different studies to be involved in extracellular matrix remodeling.