NeurometPlus

Incidence

CHARGE association is rare with an incidence of about 1 in 8,500 to 10,000 newborns. Its prevalence in older children will be diminished by significant infant mortality. More than 250 cases reported, As of 2005, the highest prevalence was found in Canada and estimated at 1 in 8,500 live births, as of 2009 it was the leading cause of congenital deafblindness in the US. (Update: September 2017/ MGJM)

Clinical Characteristics

CHARGE is an acronym in which each letter refers to a characteristic problem in affected children. C refers to Coloboma, a cleft in the pupil and/or retina of the eye; H to Heart disease that includes holes in the atrial or ventricular septum; A to Atresia choanae, a narrowing or occlusion of the nasal passages in the skull; R to Retarded growth and development, G to Genital anomalies that are particularly obvious in males with small penis and undescended testicles; E to Ear anomalies. The cause or causes of the defects in CHARGE association are not defined, and there is no specific genetic or chromosomal test. The diagnosis is made by noting the combination of congenital anomalies with growth and developmental delay, and other conditions with similar types of anomalies must be excluded. Mutations in the CHD7 gene cause most cases of CHARGE syndrome. The CHD7 gene provides instructions for making a protein that regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. Most mutations in the CHD7 gene lead to the production of an abnormal CHD7 protein that is broken down prematurely. Shortage of this protein is thought to disrupt chromatin remodeling and the regulation of gene expression. Changes in gene expression during embryonic development likely cause the signs and symptoms of CHARGE syndrome. A small percentage of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. Some of them may have a genetic change affecting the CHD7 gene that has not been found, and others may have a change in a different gene, although additional genes associated with CHARGE syndrome have not been identified. A chromosome study is usually required to eliminate other conditions with eye coloboma and heart defects such as trisomy 13 or duplications of chromosome 22. Some patients with CHARGE association have had the absent thymus, small jaw and defective thymus (immune) function that is typical of DiGeorge anomaly. Since certain patients with DiGeorge anomaly have subtle deletions of the proximal long arm of chromosome 22, a specific fluorescent (FISH) study for these chromosome 22 deletions may be considered in selected individuals with CHARGE association. Intrauterine growth retardation resulting in low birth weight occurs in 16% of patients; 92% have growth delay during the first year of life.

Precipitants

no

Provocation Tests

none

Diagnostic Procedures

Genetic testing for CHARGE syndrome involves specific genetic testing for the CHD7 gene. The test is available at most major genetic testing laboratories. CHARGE syndrome is a clinical diagnosis, which means genetic testing is not required in order to make the diagnosis. Rather, the diagnosis can be made based on clinical features alone. The diagnosis is made by noting the combination of congenital anomalies with growth and developmental delay.