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The spectrum of cochlear malformations in CHARGE syndrome and insights into the role of the CHD7 gene during embryogenesis of the inner ear

  • Paediatric Neuroradiology
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Abstract

Purpose

We reviewed the genotypes and the imaging appearances of cochleae in CHARGE patients from two large tertiary centres and analysed the observed cochlear anomalies, providing detailed anatomical description and a grading system. The goal was to gain insight into the spectrum of cochlear anomalies in CHARGE syndrome, and thus, in the role of the CHD7 gene in otic vesicle development.

Methods

We retrospectively reviewed CT and/or MR imaging of CHARGE patients referred to our institutions between 2005 and 2022. Cochlear morphology was analysed and, when abnormal, divided into 3 groups in order of progressive severity. Other radiological findings in the temporal bone were also recorded. Comparison with the existing classification system of cochlear malformation was also attempted.

Results

Cochlear morphology in our CHARGE cohort ranged from normal to extreme hypoplasia. The most common phenotype was cochlear hypoplasia in which the basal turn was relatively preserved, and the upper turns were underdeveloped. All patients in the cohort had absent or markedly hypoplastic semicircular canals and small, misshapen vestibules. Aside from a stenotic cochlear aperture (fossette) being associated with a hypoplastic or absent cochlear nerve, there was no consistent relationship between cochlear nerve status (normal, hypoplasia, or aplasia) and cochlear morphology.

Conclusion

Cochlear morphology in CHARGE syndrome is variable. Whenever the cochlea was abnormal, it was almost invariably hypoplastic. This may shed light on the role of CHD7 in cochlear development. Accurate morphological description of the cochlea contributes to proper clinical diagnosis and is important for planning surgical treatment options.

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Funding

Research reported in this publication was supported by the National Institute of Health Biomedical Research Center at Great Ormond Street Hospital, London UK (unfunded).

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Authors and Affiliations

  1. Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond St. London, London, WC1N3JH, UK

    Martin A. Lewis & Felice D’Arco

  2. Department of Radiology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA

    Amy Juliano

  3. Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Caroline Robson

  4. Department of Clinical Genetics, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK

    Emma Clement

  5. Department of Audiological Medicine, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK

    Robert Nash & Kaukab Rajput

  6. Department of Radiology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

    Felice D’Arco

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  1. Martin A. Lewis
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  2. Amy Juliano
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  3. Caroline Robson
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  4. Emma Clement
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  7. Felice D’Arco
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Contributions

Martin A Lewis1, Amy Juliano, and Felice D’Arco: conceived the study, did the data analysis, wrote the manuscript. Caroline Robson: revised the manuscript. Emma Clement, Robert Nash, Kaukab Rajput: helped in the data collection and in writing the manuscript.

Corresponding author

Correspondence to Felice D’Arco.

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The authors declare that they have no conflict of interest.

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All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional research committee (Clinical Research Adoption Committee) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Standard clinical informed consent was obtained at the time of the scan. Informed consent for this specific study was not applicable given the retrospective nature of this research.

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Martin A. Lewis and Amy Juliano shared first authorship.

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Lewis, M.A., Juliano, A., Robson, C. et al. The spectrum of cochlear malformations in CHARGE syndrome and insights into the role of the CHD7 gene during embryogenesis of the inner ear. Neuroradiology 65, 819–834 (2023). https://doi.org/10.1007/s00234-023-03118-9

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