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Cerebral cortex maldevelopment in syndromic craniosynostosis.

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Children with FGFR-related craniosynostosis have reduced cerebral cortex surface area despite normal intracranial volume, indicating maldevelopment. This highlights the need for specialized educational support in these cases.

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Syndromic craniosynostosis involves premature fusion of skull sutures, impacting brain development.
  • Fibroblast growth factor receptor (FGFR) and TWIST1 gene mutations are common causes of syndromic craniosynostosis.
  • Understanding the relationship between intracranial volume (ICV) and cerebral cortical surface area (CSA) is crucial for assessing neurodevelopmental outcomes.

Purpose of the Study:

  • To investigate the relationship between CSA and ICV in patients with syndromic craniosynostosis.
  • To compare CSA scaling in FGFR-related craniosynostosis versus TWIST1-related craniosynostosis and controls.
  • To identify specific brain regions affected by maldevelopment in FGFR-related craniosynostosis.

Main Methods:

  • Retrospective review of 140 patients with syndromic craniosynostosis and 36 controls.
  • Analysis of 203 magnetic resonance imaging (MRI) scans using FreeSurfer pipeline for ICV and CSA quantification.
  • Mixed regression modeling to determine scaling coefficients, accounting for age, sex, and syndrome.

Main Results:

  • Patients with FGFR mutations had significantly greater mean ICV compared to TWIST1 and control groups.
  • CSA scaling to ICV was reduced in FGFR patients (exponent 0.68) compared to TWIST1 (0.81) and controls (0.77).
  • Reduced scaling was particularly noted in the parietal and occipital lobes of FGFR patients, with higher rates of modified learning environments.

Conclusions:

  • FGFR-mediated craniosynostosis is associated with reduced CSA development despite adequate ICV, suggesting cortical maldevelopment.
  • Parietal and occipital lobe development appears disproportionately affected in FGFR-related craniosynostosis.
  • Increased need for modified educational support in patients with FGFR-related craniosynostosis warrants further investigation.