SSBP INFORMATION SHEET
CHARGE SYNDROME (OR ASSOCIATION)

First Description: Hall (1979)

Incidence/prevalence:
Most common estimate is 1/10-12,000 births. A recent epidemiological survey in Canada reported 1:8,500 (Issekutz, Graham, Prasad, Smith, & Blake, 2005).

Genetics/aetiology:
May be genetically heterogeneous. Rare and variable chromosomal aberrations found in a few individuals (Lalani, et al., 2005). Recently, mutations to the CHD7 gene have been established as one cause of CHARGE (Vissers, et al, August, 2004). The mutations are largely stop mutations, resulting in a preliminary stop of the transcription of the gene and a too short CHD7 protein. This protein might be either non-functional or might not be transported. Since the CHD7 gene regulates the expression of other genes the effect can be quite variable.

Physical phenotype:
The acronym was suggested by Pagon and colleagues (1981) based on common features: C – coloboma of the eye (missing part of iris and/or retina); H – heart defects; A – atresia of the choanae (bony or membranous blocking of nasal passage); R – retardation of growth and/or development; G – genitourinary anomalies; E – ear anomalies and/or deafness. While all six features may appear, there is wide variation in both occurrence and severity. This has led to a more refined diagnostic system (Blake et al, 1998) with four major features (coloboma, choanal atresia, cranial nerve dysfunction, characteristic CHARGE ear) and a number of minor anomalies. Diagnosis is based on 3 major or 2 major and 2 minor.

CHARGE is asymmetrical. Two recent studies have found the left side to be more often affected than the right. Diagnosis is difficult because there is great variability in presence and severity of the features.

CHARGE has become the most common cause of congenital deaf-blindness (after "other" and "unknown"). Vestibular difficulties are present due to missing or malformed semi-circular canals and otoliths. Swallowing difficulties are common due to cranial nerve dysfunction. Other problems include gastroesophageal reflux, airway difficulties, chronic otitis media, sinusitis, detached retina, scoliosis, chronic constipation with megacolon, and sleep disturbances.

Cognitive characteristics:
There is considerable variability, with some children very developmentally delayed, and others attending college. One longitudinal study Salem-Hartshorne & Jacob, 2005) found average adaptive behaviour in the low normal range, with little change over four years. Deficits in executive function have been suggested (Nicholas, 2005).

Behavioural characteristics:
There is variability in the presence of behavioural difficulties (Hartshorne & Cypher, 2004). The behaviours have led to diagnoses of autism, attention deficit/hyperactivity disorder, obsessive-compulsive disorder, and tic disorder. Sensory deficits and regulation difficulties may impact behaviour (Brown, 2005).

References:
Blake KD, Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS, Lin AE, Graham JM, Jr. 1998. CHARGE association: an update and review for the primary pediatrician. Clin Pediatr (Phila) 37(3):159-73.

Brown D. 2005. CHARGE syndrome behaviors : Challenges or adaptations? Am J Med Genet 133A:268-272.

Hall B. 1979. Choanal atresia and associated multiple anomalies. J Pediatrics 95: 395-98.

Hartshorne TS, Cypher AD. 2004. Challenging behavior in CHARGE Syndrome. Ment Health Aspec Dev Disabil. 7(2):41-52.

Issekutz KA, Graham JM Jr, Prasad C, Smith IM, Blake KD. 2005. An epidemiological analysis of CHARGE syndrome: Preliminary results from a Canadian study. Am J Med Genet 133A:309-317.

Lalani SR, Safiullah AM, Fernbach SD, Phillips M, Bacino CA, Molinari LM, Glass NL, Towbin JA, Craigen WJ, Belmont JW. 2005. BMC Med Genet (BMC medical genetics [electronic resource].) 2005 Feb 14; 6(1): 8

Nicholas J. 2005. Can specific deficits in executive functioning explain the behavioral characteristics of CHARGE syndrome: A case study. Am J Med Genet 133A:300-305.

Pagon RA, Graham JM, Jr., Zonana J, Yong SL. 1981. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr 99(2):223-7.

Salem Hartshorne N. Jacob S. 2005. Adaptive behavior in children with CHARGE syndrome. Am J Med Genet 133A:262-267.

Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG. 2004. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet (Nature genetics.) 36(9):955-7.

Tim Hartshorne, 2005

Return to 'Syndromes' index page