Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis

Andrea Thomas, Jane Waite, Caitlin Williams, Jeremy Kirk, Chris Oliver, Caroline Richards

Research output: Contribution to journalReview articlepeer-review


Background: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors.
Methods: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics.
Results: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties.
Conclusions: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.
Original languageEnglish
Article number49
Number of pages20
JournalJournal of Neurodevelopmental Disorders
Publication statusPublished - 31 Aug 2022

Bibliographical note

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Funding Information:
This research was funded by the University of Birmingham, Birmingham Women’s and Children’s NHS Foundation Trust and Cerebra.


  • CHARGE syndrome
  • Sensory impairment
  • Behavioural phenotype
  • Aggressive behaviour
  • Self-injurious behaviour
  • Sleep
  • Intellectual disability


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