Molecular Insights into Craniosynostosis: A Review

Abstract

Introduction and Purpose Craniosynostosis (CS), the premature fusion of one or more calvarial sutures, is a common congenital skull malformation affecting 1 in 2000–2500 live births. The calvarial sutures, including the metopic, lambdoid, coronal, and sagittal, are essential for skull and brain development. Premature fusion can cause skull deformities, increased intracranial pressure, cortical lesions, intellectual disabilities, or sensory impairments. This study reviews the clinical and molecular mechanisms of CS, explores syndromic and non-syndromic forms, and discusses advances in diagnostics and treatment. Material and Methods A comprehensive literature review examined CS's clinical presentation, genetic basis, and molecular pathways. Syndromic forms linked to FGFR1, FGFR2, FGFR3, and TWIST1 were analyzed alongside insights into non-syndromic CS. Current treatment strategies and future diagnostic directions were evaluated. Description of the State of Knowledge CS is a heterogeneous condition with syndromic and non-syndromic variants. Syndromic CS is linked to over 180 genetic disorders, often inherited dominantly, and includes syndromes like Apert, Crouzon, and Saethre-Chotzen, associated with FGFR and TWIST1 mutations. These syndromes exhibit diverse phenotypes, many unrelated to CS. Non-syndromic CS's molecular mechanisms remain less understood, but recent research highlights novel genetic contributors and signaling pathways, offering therapeutic insights. Conclusions CS is a complex condition with clinical and genetic variability. Syndromic CS is well-studied, while non-syndromic forms need further research. Advances in genetic understanding and signaling pathways provide new insights into CS pathogenesis. Integrating molecular diagnostics with surgical treatment could enhance management. Future research should uncover the genetic basis of CS to improve diagnostics and enable innovative therapies.

Keywords

• Craniosynostosis
• skull sutures
• premature suture fusion
• cranial deformity