Facial skeleton dysmorphology in syndromic craniosynostosis: differences between FGFR2 and no-FGFR2-related syndromes and relationship with skull base and facial sutural patterns.

Abstract

To assess the role of FGFR2 mutations and sutural synostotic patterns on facial skeleton dysmorphology in children with syndromic craniosynostosis. Preoperative high-resolution CT images in 39 infants with syndromic craniosynostosis were evaluated. Patients were divided into infants with and without FGFR2 mutations; each group was split according to synostotic involvement of minor sutures/synchondroses: isolated or combined involvement of middle (MCF) and posterior cranial fossae (PCF). Quantitative analysis of the midface and mandible measures was performed. Each subgroup was compared with a group of age-matched healthy subjects. Twenty-four patients with FGFR2 related syndromes were clustered in 3 subgroups: MCF + PCF (8 patients, 5.4 ± 1.75months), MCF (8 patients, 3.62 ± 1.68months), and PCF (8 patients, 2.75 ± 0.46months). Fifteen no-FGFR2 patients were clustered in 2 subgroups: MCF + PCF (7 patients, 9.42 ± 0.78months) and PCF (8 patients, 7.37 ± 2.92months). Both FGFR2 and no-FGFR2 groups with involvement of minor sutures coursing in MCF showed more facial sutural synostoses. Children with minor suture/synchondrosis synostosis of MCF (MCF-PCF and MCF subgroups) showed altered position of glenoid fossa and mandibular inclination ([Formula: see text]), but children in the FGFR2 group had also reduced midfacial depth and maxillary length ([Formula: see text]). Children with minor suture/synchondrosis synostosis of PCF (PCF subgroups) had reduced posterior mandibular height, but those children in the FGFR2 group also showed reduced intergonion distance ([Formula: see text]). In children with syndromic craniosynostosis, both skull base and facial suture synostosis affect facial dysmorphology/hypoplasia. FGFR2 mutations may worsen facial hypoplasia both acting on bone development and causing an earlier premature closure of facial sutures.