Genetics Northern California

CHARGE syndrome

CHARGE Syndrome is a specific set of birth defects that tend to occur together. CHARGE is an acronym for the common clinical features often associated with the syndrome. It occurs in roughly 1 in every 10,000 to 12,000 births. The frequency is the same in males and females.  

C - Coloboma
Coloboma is a defect caused by incomplete formation of the eye. It can occur in one or more areas of the eye including the iris, the retina, or the disc. It may result in the loss of vision and heightened sensitivity to bright light.

H - Heart Defects
Eight out of ten children born with CHARGE Syndrome have some form of heart defect. These abnormalities are highly varied; they range from small holes between the lower chambers of the heart that close naturally to potentially life threatening abnormalities that require open heart surgery.

A - Atresia of the Choanae
Choanae atresia is the complete blockage of the back of the nasal passage. It can be one-sided (unilateral) or two-sided (bilateral). These blockages cause the inability to breathe and may require an urgent operation.

R - Retardation of Growth and Development
This category of diagnostic criteria is subdivided into two parts: growth retardation and developmental delay. Although the birth weights of children with CHARGE Syndrome are usually within normal limits, failure to thrive during the first two years of life is common. The poor growth is related to feeding problems as well as hormonal imbalances in a minority of cases. The developmental delay is usually related to sensory loss including vision and hearing. Some children have mental retardation that can range from mild to severe.

G -  Genital Hypoplasia and Urinary Abnormalities 
Many boys with CHARGE syndrome have a small penis and/or undescended testes. Girls may have small or absent labia. Both sexes may require hormone therapy in order to achieve puberty. Affected children can also have kidney and urinary problems.

E - Ear Abnormalities and Hearing Loss
Almost all children with CHARGE Syndrome have ear abnormalities. Many will have deformed outer ears that appear cupped. Middle and inner ear abnormalities occur frequently as well. In about 80-85% of children, hearing loss is prevalent. Establishing and maintaining balance may be a problem for some children.

Children with CHARGE syndrome usually have a number of different abnormalities. In addition to the findings that give the conditions its name, there are other problems that can frequently be seen in individuals with CHARGE syndrome. Some of these include postnatal growth problems, cleft lip and/or palate, immunity problems, facial paralysis, seizures, difficulties swallowing, abnormalities of the pituitary gland, tracheoesophageal fistula (an abnormal connection between the trachea or wind pipe and the esophagus or food pipe), and tracheosophageal atresia (the esophagus ends in a pouch instead of connecting to the stomach).

Once the major medical problems have been addressed, there can be ongoing issues related to growth, sexual maturation, intelligence, vision, hearing, speech and language development, and general health that will need to be addressed throughout life.

Diagnosis
The diagnosis is made by clinical examination. At least four out of the six main characteristics must be present in order to diagnose a child with CHARGE Syndrome.

Cause 
It has recently been found that mutations (changes) in a gene called CDH7 causes the features of CHARGE syndrome in about 60% of individuals with this diagnosis. CHARGE syndrome usually happens randomly due to a de novo mutation in the gene, but there have been a minority of cases where the altered gene is inherited from a parent.  Other conditions with overlapping features include VATER association, Velocardiofacial Syndrome, and prenatal retinoic acid (Accutane) exposure.

Treatment/Services
Children with CHARGE syndrome require a great deal of medical management. Surgical treatment may be required to repair birth defetcs related to the condition, such as a heart defect, choanal atresia, problems with the gastrointestinal tract, or cleft lip-palate.  Many of the surgical procedures can be performed when the child is an infant; other clinical features may have to be addressed later in life. It is important for a child with CHARGE syndrome to be  evaluated regularly by a skilled and trusted team of specialists to ensure that all medical concerns are being addressed and treated accordingly.

The impact of CHARGE syndrome on the child and family can be emotionally, physically, and financially taxing. There is a great need for information and support; speaking to a social worker and contacting other resources can be greatly beneficial.  

RESOURCES

The CHARGE Syndrome Foundation - Provides support to individuals with CHARGE and their families. Site also includes detailed information about CHARGE syndrome.

___________________________________________________________________

References:
CHARGE Syndrome: An Update; D Sanlaville and A Verloes; European Journal of Human Genetics (2007) 15,389–399

Last Updated: July 23, 2009 by Kimberly Barr, M.S.
Last Reviewed: July 23, 2009 by Kimberly Barr, M.S.