Current Understanding of Crouzon Syndrome Pathophysiology and New Therapeutic Approaches

Crouzon syndrome (CS) is a rare genetic disorder characterized by the premature fusion of cranial sutures, leading to craniofacial abnormalities and potential neurological complications. CS is caused primarily by gain-of-function mutations in the FGFR2 gene and, less commonly, by mutations in the FGFR3 gene (specifically associated with CS with acanthosis nigricans). Managing CS requires a multidisciplinary approach, combining early and later surgical interventions to prevent intracranial hypertension and correct craniofacial deformities, along with ongoing care to address associated complications. Recent advancements in CS classification on the basis of cranial suture involvement have refined phenotype-genotype correlations, improving personalized therapeutic strategies. This review aims to provide a comprehensive and updated overview of CS, including detailed insights into molecular genetics and biological mechanisms underlying its pathophysiology, and a depiction of the clinical features, diagnosis, and surgical aspects of CS. In addition, we delve into innovative theranostic views, where molecular genetic testing allows the design of personalized noninvasive therapeutic approaches based on innovative biotechnologies, including RNA-interference molecules, pharmacological modulation of FGFR signaling pathways, and recombinant proteins. These advancements underscore the importance of integrating molecular studies into diagnostic and therapeutic protocols to increase the precision and effectiveness of nonsurgical treatments for CS.