Enhancing Predictive Tools for Skeletal Growth and Craniofacial Morphology in Syndromic Craniosynostosis: A Focus on Cranial Base Variables

<b>Background/Objectives</b>: Patients with syndromic craniosynostosis (SC) pose a significant challenge for post-operational outcomes due to the variability in craniofacial deformities and gain-of-function characteristics. This study aims to develop validated predictive tools using stable cranial base variables to predict changes in the midfacial region and explore the craniofacial morphology among patients with SC. <b>Methods</b>: This study involved 17 SC patients under 12 years old, 17 age-matched controls for morphological analysis, and 21 normal children for developing craniofacial predictive models. A stable cranial base and changeable midfacial variables were analyzed using the Mann-Whitney U test. Pearson correlation identified linear relationships between the midface and cranial base variables. Multicollinearity was checked before fitting the data with multiple linear regression for growth prediction. Model adequacy was confirmed and the 3-fold cross-validation ensured results reliability. <b>Results</b>: Patients with SC exhibited a shortened cranial base, particularly in the middle cranial fossa (S-SO), and a sharper N-S-SO and N-SO-BA angle, indicating a downward rotation and kyphosis. The midface length (ANS-PNS) and zygomatic length (ZMs-ZTi) were significantly reduced, while the midface width (ZFL-ZFR) was increased. Regression models for the midface length, width, and zygomatic length were given as follows: ANS-PNS = 23.976 + 0.139 S-N + 0.545 SO-BA - 0.120 N-S-BA + 0.078 S-SO-BA + 0.051 age (R² = 0.978, RMSE = 1.058); ZFL-ZFR = -15.618 + 0.666 S-N + 0.241 N-S-BA + 0.155 S-SO-BA + 0.121 age (R² = 0.903, RMSE = 3.158); and ZMs-ZTi = -14.403 + 0.765 SO-BA + 0.266 N-S-BA + 0.111 age (R² = 0.878, RMSE = 3.720), respectively. <b>Conclusions</b>: The proposed models have potential applications for midfacial growth estimation in children with SC.