Related Experiment Video
Updated: Oct 28, 2025
Author Spotlight: Studying Clinical Characters and Epilepsy Outcomes After Frontal Disconnection in Patients with MOGHE
Published on: August 16, 2024
Cerebral cortex maldevelopment in syndromic craniosynostosis
Alexander T Wilson1,2, Bianca K Den Ottelander1, Marie-Lise C Van Veelen3
1Department of Plastic and Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.
Insights
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.
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.
Aim:
To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis.
Method:
Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo-24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log-transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome.
Results:
Mean ICV was greater in patients with FGFR (1519cm3 , SD 269cm3 , p=0.016) than in patients with TWIST1 (1304cm3 , SD 145cm3 ) or controls (1405cm3 , SD 158cm3 ). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61-0.76) in patients with FGFR compared to 0.81 (95% CI 0.50-1.12) in patients with TWIST1 and 0.77 (95% CI 0.61-0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42-0.59) and occipital (0.67, 95% CI 0.54-0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR.
Interpretation:
Despite adequate ICV in FGFR-mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR.
More Related Videos
02:42Analysis of Craniomaxillofacial Malformations in Mice Using Three-dimensional Microcomputed Tomography
Published on: January 17, 2025
13:47Ex utero Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development
Published on: April 3, 2013
Related Concept Videos
01:22Sutures of the Skull
Sutures are immobile joints between adjacent bones of the skull. The narrow gap between the bones is filled with dense, fibrous connective tissue that unites the bones. The long sutures located between the skull bones are not straight but instead follow irregular, tightly twisting paths. These twisting lines tightly...
01:14Cranial Bones: Superior and Posterior View
The frontal bone is the single bone that forms the forehead. At its anterior midline, between the eyebrows, there is a slight depression called the glabella. The frontal bone also forms the supraorbital margin of the orbit. Near the middle of this margin is the supraorbital foramen, the opening that provides passage for a sensory nerve to the forehead. The frontal bone is thickened just above each supraorbital margin,...
01:30Neurulation
01:26Cerebrum: Anatomical Overview I
01:27Cranial Bones: Lateral View
The temporal bone forms the lower lateral side of the skull. The temporal bone is subdivided into several regions. The flattened upper portion is the squamous portion of the temporal bone. Below this area and projecting anteriorly is the zygomatic process of the temporal bone, which forms the posterior portion of the zygomatic arch. Posteriorly is the mastoid portion of the temporal bone. Projecting...
01:19Cranial and Spinal Meninges
Cranial Meninges
These meningeal layers cover the cranium. The dura mater is the outermost layer of cranial meninges. It is a thick and durable membrane of dense...