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Brain structural changes in patients with cardio-facio-cutaneous syndrome: effects of BRAF gene mutation and epilepsy on brain development. A case–control study by quantitative magnetic resonance imaging

  • Paediatric Neuroradiology
  • Published:
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Abstract

Purpose

To evaluate the brain volumetric changes caused by BRAF gene mutation in non-epileptic CFC patients and the influence of the age of epilepsy onset on brain development in 2 cohorts of epileptic CFC patients.

Methods

We enrolled CFC patients carrying BRAF gene mutations without epilepsy (4 patients) and with epilepsy (16 patients). CFC epileptic patients were divided into two cohorts based on the age of seizure onset: early-age onset (7 children) and late-age onset (9 adolescents). All three cohorts of patients underwent 3D FSPGR T1-weighted imaging to assess supratentorial and infratentorial brain volumes. Moreover, for each compartment, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes were measured. All measurements were compared with those of age-matched controls without neuroimaging abnormalities.

Results

All CFC patients showed supratentorial and infratentorial WM reduction and supratentorial ventricular enlargement (p < 0.01).

However, patients with early age of epilepsy onset, compared with the other two cohorts of CFC patients, showed both GM and a more pronounced WM volume reduction (p < 0.01).

Conclusion

In non-epileptic CFC children, we demonstrated WM volumetric reduction suggesting a direct effect of BRAF gene mutation on brain development. Nevertheless, in CFC epileptic patients, the age of epilepsy onset may contribute to brain atrophy.

Brain atrophy in CFC patients, in part due to the natural history of the disease, may be worsened by epilepsy when it begins in the early ages because of interference with brain growth at that critical age of development.

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Author information

Authors and Affiliations

  1. Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Radiologia e Neuroradiologia, Polo Diagnostica per immagini, radioterapia, oncologia ed ematologia, Area diagnostica per immagini, Rome, Italy

    Rosalinda Calandrelli, Marco Panfili & Cesare Colosimo

  2. Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University, 00128, Rome, Italy

    Fabio Pilato

  3. Child Neuropsychiatry Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy

    Domenica Battaglia & Maria Luigia Gambardella

  4. Università Cattolica del Sacro Cuore, Istituto di Neuropsichiatria infantile, Rome, Italy

    Domenica Battaglia

  5. Università Cattolica del Sacro Cuore, Istituto di Radiologia, Rome, Italy

    Cesare Colosimo

Authors
  1. Rosalinda Calandrelli
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  2. Fabio Pilato
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  5. Maria Luigia Gambardella
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Contributions

Rosalinda Calandrelli: project development, data collection, manuscript writing.

Fabio Pilato: data collection, statistical analysis, manuscript writing.

Marco Panfili: data collection.

Domenica Battaglia: data collection.

Maria Luigia Gambardella: patient recruitment, drafting paper.

Cesare Colosimo: project development, manuscript writing.

All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Fabio Pilato.

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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.

Marco Panfili declares that he has no conflict of interest.

Domenica Battaglia declares that she has no conflict of interest.

Maria Luigia Gambardella declares that she has no conflict of interest.

Cesare Colosimo declares that he is a scientific consultant for Bracco Diagnostics Inc. and Bayer HealthCare.

Ethical approval

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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Informed consent was obtained from all individual participants included in the study.

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Calandrelli, R., Pilato, F., Panfili, M. et al. Brain structural changes in patients with cardio-facio-cutaneous syndrome: effects of BRAF gene mutation and epilepsy on brain development. A case–control study by quantitative magnetic resonance imaging. Neuroradiology 64, 185–195 (2022). https://doi.org/10.1007/s00234-021-02769-w

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  • DOI: https://doi.org/10.1007/s00234-021-02769-w

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