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

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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 (\(p<0.05\)), but children in the FGFR2 group had also reduced midfacial depth and maxillary length (\(p<0.05\)). 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 (\(p<0.05\)).

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.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethical approval and consent to participate.

We declare that all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Authors and Affiliations

  1. Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 1, Rome, 00168, Italy

    Rosalinda Calandrelli, Gabriella D’Apolito & Cesare Colosimo

  2. Unit of Neurology, Department of Medicine, Neurophysiology, Università Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy

    Fabio Pilato

  3. Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy

    Fabio Pilato

  4. Pediatric Neurosurgery, Neurosurgery Department, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 1, Rome, 00168, Italy

    Luca Massimi

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Contributions

R.C.: project development, data collection, manuscript writing. F.P.: data collection, statistical analysis, manuscript writing. L.M.: data collection. G.D.: data collection. C.C.: project development, manuscript writing. All authors read and approved the final manuscript.

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Correspondence to Rosalinda Calandrelli.

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Conflict of interest

Rosalinda Calandrelli declares that she has no conflict of interest. Fabio Pilato declares that he has no conflict of interest. Luca Massimi declares that he has no conflict of interest. Gabriella D’Apolito declares that she has no conflict of interest. Cesare Colosimo declares that he is a scientific consultant for Bracco Diagnostics Inc. and Bayer HealthCare.

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Calandrelli, R., Pilato, F., Massimi, L. et al. Facial skeleton dysmorphology in syndromic craniosynostosis: differences between FGFR2 and no-FGFR2-related syndromes and relationship with skull base and facial sutural patterns. Childs Nerv Syst 39, 3235–3247 (2023). https://doi.org/10.1007/s00381-023-05962-9

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