The influence of closed sutures on cranial morphology in Apert and Crouzon syndromes: A quantitative analysis.

Abstract

Craniosynostoses are congenital conditions characterized by premature suture fusions, altering skull growth and potentially impairing neurological function. Apert and Crouzon syndromes, both linked to FGFR2 mutations, share features but differ in their patterns of suture fusion and cranial deformation. This study quantitatively analyzes, with a high-resolution 3D morphometric analysis, global cranial morphology in syndromic craniosynostoses, comparing Crouzon and Apert syndromes to controls using standard medical CT scans; 72 unoperated patients with syndromic craniosynostoses (51 with Crouzon syndrome, 21 with Apert syndrome) and 289 controls were analyzed. Cranial vault segmentation was performed, and surfaces were rigidly aligned. Non-rigid registration enabled standardized mesh generation, with semi-landmarks extracted for shape analysis. Age-related shape variation was mitigated before analysis identified key morphological variation axes. Statistical comparisons revealed significant shape differences. Apert patients displayed a distinct turricephalic vault morphology with increased cranial height and reduced width, whereas Crouzon patients were more variable, with a moderate brachycephalic shape in bicoronal fusion and reduced vault distortion in pansynostosis. Unsupervised clustering showed clear morphometric separation of Apert patients, while Crouzon patients exhibited greater heterogeneity. Subgroups within Crouzon syndrome revealed specific deformation patterns associated with suture closure configurations. These findings refine our understanding of cranial shape variations in syndromic craniosynostoses and emphasize the need for integrating advanced morphometric analyses into clinical assessments. The distinct morphological signatures identified in Apert syndrome and Crouzon syndrome subgroups could inform personalized surgical planning and enhance phenotypic-genotypic correlations.