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

J Neurodev Disord. 2022 Aug 31;14(1):49. doi: 10.1186/s11689-022-09459-5.


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.

Keywords: Aggressive behaviour; Behavioural phenotype; CHARGE syndrome; Intellectual disability; Self-injurious behaviour; Sensory impairment; Sleep.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression
  • CHARGE Syndrome* / complications
  • CHARGE Syndrome* / epidemiology
  • Humans
  • Intellectual Disability* / complications
  • Intellectual Disability* / epidemiology
  • Intellectual Disability* / psychology
  • Self-Injurious Behavior* / epidemiology
  • Self-Injurious Behavior* / psychology
  • Sleep Wake Disorders*