CHARGE syndrome

Department of Pediatrics, IWK Health Centre, Dalhousie University, Canada.
Orphanet Journal of Rare Diseases (Impact Factor: 3.36). 02/2006; 1(1, article 34):34. DOI: 10.1186/1750-1172-1-34
Source: PubMed


CHARGE syndrome was initially defined as a non-random association of anomalies (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with all four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome. However, there have been individuals genetically identified with CHARGE syndrome without the classical choanal atresia and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1-1.2/10,000 and depends on professional recognition. Coloboma mainly affects the retina. Major and minor congenital heart defects (the commonest cyanotic heart defect is tetralogy of Fallot) occur in 75-80% of patients. Choanal atresia may be membranous or bony; bilateral or unilateral. Mental retardation is variable with intelligence quotients (IQ) ranging from normal to profound retardation. Under-development of the external genitalia is a common finding in males but it is less apparent in females. Ear abnormalities include a classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness that ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the CHD7 gene (member of the chromodomain helicase DNA protein family) are detected in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome require intensive medical management as well as numerous surgical interventions. They also need multidisciplinary follow up. Some of the hidden issues of CHARGE syndrome are often forgotten, one being the feeding adaptation of these children, which needs an early aggressive approach from a feeding team. As the child develops, challenging behaviors become more common and require adaptation of educational and therapeutic services, including behavioral and pharmacological interventions.

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    • "The difficulty for clinical diagnosis of CHARGE syndrome is how to differentiate from the 22q deletion syndrome, Kabuki syndrome, Velo-cardio-facial syndrome (VCFS), Cat Eye syndrome, retinoic acid embryopathy, VACTERL association and PAX2 abnormalities, which have many similar behavioral and clinical features with CHARGE. Therefore, gene analysis is the most accurate and definitive method for differential diagnosis (Blake and Prasad, 2006). The only pathogenic gene involved in CHARGE syndrome reported to date is CHD7. "
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    ABSTRACT: In Genetics Out-patient Department of Shanghai Children's Medical Center, we consulted a 3-year-old boy with multiple anomaly syndrome (congenital heart disease, cryptorchidism, congenital deafness, mental retardation, exophthalmos, laryngeal cartilage dysplasia and high arched palate). We ruled out the possibility of multiple deformities caused by genomic imbalances. The patient was then clinically considered to have CHARGE syndrome, an autosomal dominant multi-system disorder involving defects in multiple organs, and CHD7 is the only known gene associated with the syndrome. Sequencing analysis of CHD7 of the proband identified a de novo heterogeneous mutation (c.2916_2917del, p.Gln972HisfsX22), a two-nucleotide deletion causing reading frame shift and resulting in a truncated CHD7 protein. Computational structure analysis suggests that the truncated protein only contains the chromodomains of CHD7, but lacks the SWI2/SNF2-like ATPase/helicase domain and the DNA binding domain, which are indispensable for the proper function of the protein, especially on chromatin remodeling. The patient then received follow up treatment in different clinical departments in a long period. To our best knowledge, this is the first CHARGE syndrome in Chinese patients diagnosed by gene analysis. In summary, the clinical symptoms and the description of treatment in the present case, combined with genetic test and functional prediction of CHD7, are helpful for further understanding and genetic counseling of the CHARGE syndrome.
    Meta Gene 12/2014; 2:469–478. DOI:10.1016/j.mgene.2014.06.002
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    • "A diagnosis of CHARGE association should be considered in any infant with coloboma, choanal atresia, asymmetric facial palsy or classical CHARGE ears in combination with other specific congenital anomalies [1]. Individuals with all four major characteristics (the classical 4C’s: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) or three major and three minor characteristics are highly likely to have CHARGE association [1,10]. "
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    ABSTRACT: CHARGE association is characterized by ocular Coloboma, Heart malformations, choanal Atresia, Retardation of growth and development, Genital abnormalities and inner and external Ear abnormalities. Growth failure is a frequent find mainly associated with feeding difficulties or systemic diseases. To date, GH deficiency has been reported in only few patients with CHARGE association however long-term effects of GH treatment, up to final height, have never been reported. We describe a patient with CHARGE association and GH deficiency treated with GH from the age of 3 years and 10 months up to adult height.
    Italian Journal of Pediatrics 06/2014; 40(1):51. DOI:10.1186/1824-7288-40-51 · 1.52 Impact Factor
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    • "CHARGE is an acronym describing some of the main clinical features of the disease (ocular Coloboma, Heart defects, choanal Atresia, Retarded growth, Genital hypoplasia and Ear anomalies). Numerous additional features are observed in the syndrome, including hyperactive behaviour [5], nerve anomalies, cleft palate, facial asymmetry and limb deformity [6]. The extent and variability of CHARGE characteristics exemplify the importance of CHD7 in multiple developmental pathways. "
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    ABSTRACT: CHARGE syndrome is a rare human disorder caused by mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7). Characteristics of CHARGE are varied and include developmental ear and hearing anomalies. Here we report a novel mouse model of CHD7 dysfunction, termed Looper. The Looper strain harbours a nonsense mutation (c.5690C>A, p.S1897X) within the Chd7 gene. Looper mice exhibit many of the clinical features of the human syndrome, consistent with previously reported CHARGE models, including growth retardation, facial asymmetry, vestibular defects, eye anomalies, hyperactivity, ossicle malformation, hearing loss and vestibular dysfunction. Looper mice display an otosclerosis-like fusion of the stapes footplate to the cochlear oval window and blepharoconjunctivitis but not coloboma. Looper mice are hyperactive and have vestibular dysfunction but do not display motor impairment.
    PLoS ONE 05/2014; 9(5):e97559. DOI:10.1371/journal.pone.0097559 · 3.23 Impact Factor
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