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

ABSTRACT

PURPOSE: To assess the role of FGFR2 mutations and sutural synostotic patterns on facial skeleton dysmorphology in children with syndromic craniosynostosis. METHODS: 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. RESULTS: Twenty-four patients with FGFR2 related syndromes were clustered in 3 subgroups MCF + PCF (8 patients, 5.4 ± 1.75 months), MCF (8 patients, 3.62 ± 1.68 months), and PCF (8 patients, 2.75 ± 0.46 months). Fifteen no-FGFR2 patients were clustered in 2 subgroups MCF + PCF (7 patients, 9.42 ± 0.78 months) and PCF (8 patients, 7.37 ± 2.92 months). 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]). CONCLUSIONS: 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.