Charge Syndrome Health Article

Definition

CHARGE syndrome, also known as CHARGE association, is a group of major and minor malformations that have been observed to occur together more frequently than expected by chance. The name of the syndrome is an acronym for some of its features, and each letter stands for the following conditions:

• C—Coloboma and/or cranial nerves
• H—Heart defects
• A—Atresia choanae,
• R—Retarded growth and development
• G—Genital anomalies
• E—Ear anomalies

While these features have classically been used for identification of affected individuals, many other malformations and medical problems have been observed to occur with this syndrome.

Description

CHARGE syndrome was first described in 1979 as an association of multiple congenital anomalies, all of which included choanal atresia, meaning the blocking of the choanae, the passages from the back of the nose to the throat which allow breathing through the nose. Soon after, several other papers were published describing similar patients who all had both choanal atresia and coloboma, that is a cleft or failure to close off the eyeball. It was in 1981 that the CHARGE acronym was proposed to describe the features of the condition. Due to the large number of patients described since 1979, many physicians now regard CHARGE association as a recognizable syndrome. However, the cause for the condition remains unclear. It is believed that perhaps a new dominant change in a gene is the cause for many cases. There have been a few familial cases but most cases are sporadic. Crucial development of the choanoa, heart, ear and other organs occurs 35-45 days after conception and any disruption in development during this time is believed to lead to many of the features of the syndrome.

Infants with CHARGE syndrome generally have difficulty with feeding and most of those affected have mental retardation. About half die during the first year of life from respiratory insufficiency, central nervous system (CNS) malformations, and bilateral choanal atresia.

Genetic profil

Most cases of CHARGE syndrome are sporadic, meaning that they occur in a random or isolated way. However, reports of parent-to-child transmission of the condition indicate an autosomal dominant type of inheritance. There have also been cases in which a parent with one or two features of CHARGE had a child with enough features to fit the diagnosis. These families may demonstrate variable expressivity of a dominant gene. In addition, there have been a few cases of siblings affected, suggesting the possible presence of a mixture of cell types (germ line mosaicism) in a parent for a dominant mutation. Therefore, the recurrence risk for healthy parents of an affected child would be low, but not negligible.

Twin studies are often used to determine if the occurrence of a condition has a strong genetic component. One such study compared a pair of monozygotic twins, meaning identical twins resulting from a single zygote (fertilized egg that leads to the birth of two individuals), who were both affected with CHARGE syndrome and a pair of dizygotic twins, meaning twins that result from fertilization of two different eggs, of whom only one had the syndrome. Since monozygotic twins are roughly 100% genetically identical, this supports the idea that there is a strong genetic factor involved in CHARGE syndrome. Other interesting observations include slightly increased paternal age in sporadic cases. The mean paternal age in one study was 34 years as opposed to 30 years in a control group. Increased paternal age has been known to be associated with the increased occurrence of new dominant mutations in offspring.

Several patients with various chromosome defects have been diagnosed with CHARGE syndrome, again pointing to genetic factors as a cause. These cases of chromosomal abnormalities point to particular genes that should be further studied. In addition, some patients with CHARGE syndrome also have features of another condition called Di George sequence which involves an immune deficiency, characteristic heart abnormalities and distinct craniofacial features. Many patients with Di George sequence have a missing chromosome 22q11. Therefore, newly diagnosed cases of CHARGE syndrome should have chromosome studies as well as molecular testing.

Demographics

The incidence of CHARGE syndrome is approximately one in 10,000. However, this is probably an underestimate of the true number of people affected. The incidence is likely to increase as the diagnostic features of the condition are refined and milder cases are diagnosed. CHARGE syndrome affects males more seriously than females, resulting in a higher number of females who survive. The cause of this is unclear. The syndrome has not been reported more often in any particular race or geographic area.

Signs and symptoms

CHARGE syndrome is believed to be caused by a disruption of fetal growth during the first three months of pregnancy and affecting many different organ systems undergoing development at that time.