Related Experiment Video
Updated: Jan 18, 2026
08:03
Midface Hypoplasia and Cranial Base Morphology in Syndromic Craniosynostosis: A Comparative Analysis Study Using a Predictive Regression Model
Published on: November 4, 2025
259
Impact of SMAD6 Variants on Neurodevelopment in Craniosynostosis
Isabelle Verlut1, Sofia Guernouche1, Massimiliano Rossi2
1Department of Pediatric Neurosurgery, French Referral Center for Craniosynostosis, Hôpital Femme Mère-Enfant Hospices Civils de Lyon, University of Lyon 1, INSERM.
The Journal of Craniofacial Surgery
|June 9, 2025
Summary
Pathogenic Smad6 variants are linked to craniosynostosis and potential developmental delays. Early neuropsychological follow-up and therapies help most children with Smad6 variants achieve normalized developmental scores.
Area of Science:
- Genetics
- Developmental Biology
- Pediatric Neurosurgery
Background:
- Pathogenic variants in the Smad6 gene are associated with midline craniosynostosis, increasing risks for syndromic and nonsyndromic presentations.
- Craniosynostosis, regardless of surgical intervention, can be linked to developmental delays in affected children.
Purpose of the Study:
- To evaluate the developmental outcomes in pediatric patients with craniosynostosis who carry Smad6 variants.
- To assess the impact of Smad6 gene variants on neuropsychological development post-craniosynostosis surgery.
Main Methods:
- A cohort of children undergoing craniosynostosis surgery between 2018-2023 at Lyon University Hospital was studied.
- Post-surgery, children with Smad6 variants underwent neuropsychological evaluations by a multidisciplinary team.
- Evaluations included neurosurgeons, clinical geneticists, and neuropsychologists to assess developmental trajectories.
Main Results:
- Eleven out of 249 craniosynostosis patients had Smad6 variants, presenting with various skull deformities (trigonocephaly, scaphocephaly, oxycephaly).
- No cardiac abnormalities were observed in these patients.
- Eight children showed mild delays in walking and/or language acquisition; most benefited from specialized care, with only one experiencing significant schooling difficulties.
Conclusions:
- Neuropsychological follow-up is essential for children with craniosynostosis and Smad6 variants.
- While most patients exhibit mild to moderate effects that improve with therapy, the combined impact of Smad6 with other variants warrants further investigation.
- Early intervention strategies are critical for optimizing cognitive and behavioral outcomes in this patient group.
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