The normal development of cranial primordia and orofacial structures involves fundamental processes in which growth, morphogenesis, and cell differentiation take place and interactions between extracellular matrix (ECM) components,
growth factors and embryonic tissues are involved. Biochemical and molecular aspects of craniofacial development, such as the
biological regulation of normal or premature cranial suture fusion, has just begun to be understood, thanks mainly to studies performed in the last decade. Several mutations has been identified in both syndromic and non-syndromic
craniosynostosis patients throwing new light onto the etiology, classification and developmental pathology of these diseases. In the more common
craniosynostosis syndromes and other skeletal
growth disorders, the mutations were identified in the genes encoding
fibroblast growth factor receptor types 1-3 (FGFR1, 2 and 3) where they are dominantly acting and affect specific and important protein binding domain. The unregulated FGF signaling during intramembranous ossification is associated to the Apert and
Crouzon syndrome. The non syndromic cleft of the lip and/or palate (CLP) has a more complex genetic background if compared to
craniosynostosis syndrome because of the number of involved genes and type of inheritance. Moreover, the influence of environmental factor makes difficult to clarify the primary causes of this malformation. ECM represents cell environment and results mainly composed by
collagens,
fibronectin,
proteoglycans (PG) and hyaluronate (HA). Cooperative effects of ECM and
growth factors regulate regional matrix production during the morphogenetic events, connective tissue remodelling and pathological states. In the present review we summarize the studies we performed in the last years to better clarify the role of ECM and
growth factors in the etiology and pathogenesis of
craniosynostosis and CLP diseases.