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

Abstract

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.

Atypical mandibulofacial dysostosis with microcephaly diagnosed through the identification of a novel pathogenic mutation in EFTUD2

“…However, these criteria are still too broad to exclude some phenotypically similar syndromes (Table 1 ). By comparing various mandibulofacial dysostosis syndromes, we aimed to identify the most characteristic manifestations to help in diagnosing MFDM (Table 1 ) (Abell et al., 2021 ; Beleza‐Meireles et al., 2015 ; Lehalle et al., 2014 ; Marszalek‐Kruk et al., 2021 ; Thomas et al., 2022 ; Yu et al., 2018 ). In the reported MFDM cases validated with EFTUD2 mutations, the most frequent phenotypes were micrognathia of variable severity, external ear anomalies and malar hypoplasia.…”

“… e Reviewed by Thomas et al. ( 2022 ). f Symptoms including astigmatism, myopia, hypermetropia, strabismus, epicanthic folds, lacrimal duct stenosis and epibulbar dermoid.…”

Case report: Functional characterization of a novel CHD7 intronic variant in patients with CHARGE syndrome

“…Both patients do not satisfy all the criteria for typical CHARGE syndrome and would be classified as Atypical or Partial cases of the Syndrome ( Verloes, 2005 ). The occurrence of atypical phenotypes associated with pathogenic CHD7 variants is frequent and well documented ( Hale et al, 2016 ; Legendre et al, 2017 ; Thomas et al, 2022 ). The cause of such high variability seen in CHARGE syndrome is unknown; it is most likely that differences in the individual genetic backgrounds are sufficient to modulate phenotypic expression, but this remains an area for future studies.…”

Cognitive potential of children and adolescents with CHARGE syndrome and deafblindness

“…Literature addressing individuals with CHARGE underlines their inherent compensatory capacity and latent developmental potential in functions and ability level [ 10 , 20 – 22 ]. However, like other rare disorders methodological issues impede quantitative behavioural studies [ 23 , 24 ]. In addition to the sample size challenges, most psychometric measures rely on operative primary senses, which excludes many individuals with combined auditory and visual impairments since enhancing accessibility impact the validity of findings.…”

“…In addition to the sample size challenges, most psychometric measures rely on operative primary senses, which excludes many individuals with combined auditory and visual impairments since enhancing accessibility impact the validity of findings. Accordingly, few quantitative studies involving performance-based assessment exist [ 24 ].…”