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Non-syndromic craniosynostosis

Nature Reviews Disease Primers volume 11, Article number: 24 (2025) Cite this article

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Abstract

Craniosynostosis is characterized by the premature fusion of one or more major cranial sutures at birth or soon after. Single-suture non-syndromic craniosynostosis (NSC) is the most common form of craniosynostosis and includes the sagittal, metopic, unicoronal and unilambdoid subtypes. Characterized by an abnormal head shape specific to the fused suture type, NSC can cause increased intracranial pressure. Cranial sutures either originate from the neural crest or arise from mesoderm-derived mesenchymal stem cells. A mixture of environmental and genetic factors contributes to NSC, with genetic causes following a largely polygenic model. Physical examination is used to identify the majority of patients, but accompanying radiographic imaging can be confirmatory. The three major surgical techniques in use to treat NSC are cranial vault remodelling, strip craniectomy and spring-assisted cranioplasty. Surgical intervention is ideally performed in the first year of life, with a mortality of <1%. Health-care disparities contribute to delayed initial presentation and timely repair. Optimal timing of surgery and comparative outcomes by surgical technique remain under active study. School-age children with treated NSC on average have subtle, but lower cognitive and behavioural performance. However, patient-reported quality of life outcomes are comparable to those in control individuals.

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Fig. 1: Cranial sutures and fontanelles of the human newborn skull.
Fig. 2: Cell lineage of cranial vault bones and sutures.
Fig. 3: CT 3D images of non-syndromic craniosynostosis.
Fig. 4: Measurements for assessment of metopic craniosynostosis severity.
Fig. 5: CR and CVAI for quantifying craniosynostosis severity.
Fig. 6: Characteristics of deformational plagiocephaly and unilateral lambdoid craniosynostosis.
Fig. 7: Main surgical procedures to correct non-syndromic craniosynostosis.

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Authors and Affiliations

  1. Division of Plastic Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT, USA

    Michael Alperovich

  2. Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, Sao Paulo, Brazil

    Cristiano Tonello

  3. Child Study Center, Yale University School of Medicine, New Haven, CT, USA

    Linda C. Mayes

  4. Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Kristopher T. Kahle

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  1. Michael Alperovich
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  2. Cristiano Tonello
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  3. Linda C. Mayes
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  4. Kristopher T. Kahle
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Contributions

Introduction (M.A. and C.T.); Epidemiology (M.A. and C.T.); Mechanisms/pathophysiology (M.A. and K.T.K.); Diagnosis, screening and prevention (M.A.); Management (M.A.); Quality of life (M.A. and L.C.M.); Outlook (all authors); overview of the Primer (M.A.).

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Correspondence to Michael Alperovich.

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M.A. consults for Johnson & Johnson. The other authors declare no competing interests.

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Nature Reviews Disease Primers thanks K. B. Patel; S. P. Bartlett, who co-reviewed with P. Tolley; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Alperovich, M., Tonello, C., Mayes, L.C. et al. Non-syndromic craniosynostosis. Nat Rev Dis Primers 11, 24 (2025). https://doi.org/10.1038/s41572-025-00607-4

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