Phenotypic Characteristics and Variability in CHARGE Syndrome: A PRISMA Compliant Systematic Review and Meta-Analysis

Abstract
Background
CHARGE syndrome (OMIM #608892) 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 diagnostic signs, 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 47 eligible studies, data could be extracted for 1,583 participants. Prevalence estimates were highest for developmental delay (82%), intellectual disability (65%), aggressive behaviour (48%), self-injurious behaviour (42%) 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 diagnostic signs, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice.