Isolated frontosphenoidal craniosynostosis with pathogenic FGFR3 variant: a case report and genetic insights.

BACKGROUND

Isolated frontosphenoidal craniosynostosis (IFSC) is rare, historically misdiagnosed as coronal synostosis due to phenotypic overlap. Traditionally viewed as sporadic, its genetic basis was largely unexplored. Recent identification of pathogenic FGFR3 variants in IFSC patients challenges this view, suggesting a genetic etiology and necessitating molecular evaluation. This study aims to establish a genetic association between premature cranial suture closure and variants of the FGFR3 gene.

CASE DESCRIPTION: This case report presents a rare instance of IFSC in a 10-month-old female infant, characterized by severe plagiocephaly due to premature fusion of the frontosphenoidal suture. Through high-resolution three-dimensional computed tomography imaging, the diagnosis was confirmed, and genetic testing revealed a heterozygous pathogenic FGFR3 missense variant (c.749C>G; p.Pro250Arg), previously associated with Muenke syndrome. This finding establishes a novel genetic association for IFSC, challenging the traditional view of its sporadic nature. The patient underwent successful unilateral fronto-orbital advancement and remodeling (FOAR), resulting in significant improvement in cranial symmetry.

CONCLUSIONS

This case highlights the importance of molecular genetic testing in nonsyndromic craniosynostosis and the potential role of FGFR3 variants in IFSC. Early diagnosis and surgical intervention are crucial, advocating for a staged genetic testing approach in similar cases. These findings emphasize IFSC's genetic basis and its consideration in cranial deformity diagnoses.