CHARGE syndrome is a recognizable (genetic) pattern of birth defects which occurs in about one in every 9-10,000 births worldwide. It is an extremely complex syndrome, involving extensive medical and physical difficulties that differ from child to child. The vast majority of the time, there is no history of CHARGE syndrome or any other similar conditions in the family. Babies with CHARGE syndrome are often born with life-threatening birth defects, including complex heart defects and breathing problems. They spend many months in the hospital and undergo many surgeries and other treatments. Swallowing and breathing problems make life difficult even when they come home. Most have hearing loss, vision loss, and balance problems which delay their development and communication. All are likely to require medical and educational intervention for many years. Despite these seemingly insurmountable obstacles, children with CHARGE syndrome often far surpass their medical, physical, educational, and social expectations.
Continued research is needed to help us understand the medical and developmental challenges facing individuals with CHARGE. Better understanding will lead the way to interventions, therapies and educational strategies which can help people with CHARGE syndrome overcome many of the obstacles in their lives.
One of the hidden features of CHARGE syndrome is the determination and strong character these children display.
The name “CHARGE” was a clever way (in 1981) to refer to a newly recognized cluster of features seen in a number of children. Over the years, it has become clear that CHARGE is indeed a syndrome and at least one gene causing CHARGE syndrome has been discovered (see below). The letters in CHARGE stand for: Coloboma of the eye, Heart defects, Atresia of the choanae,Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and deafness. Those features are no longer used in making a diagnosis of CHARGE syndrome, but we’re not changing the name.
Even though a gene for CHARGE syndrome has been discovered, the gene test is very expensive and isn’t perfect -only about 2/3 of people with CHARGE have a positive gene test. Therefore, the diagnosis of CHARGE syndrome is still clinical – based on the medical features seen in the child. An evaluation for possible CHARGE syndrome should be made by a medical geneticist who is familiar with CHARGE. The clinical diagnosis is made using a combination of Major and Minor features. Major features are characteristics that are quite common in CHARGE syndrome but relatively rare in other conditions, and are, for the most part, diagnosable in the newborn period. Minor features are characteristics which are also common in CHARGE, but not quite as helpful in distinguishing CHARGE from other syndromes. They either are common in other conditions (e.g. heart defects), harder to diagnose consistently (e.g. typical CHARGE face), or may not be diagnosed until later (e.g. growth deficiency). Finally, there are “Other” features – these may be very important in terms of health and management, but are not very helpful in determining if a child has CHARGE syndrome or something else.
|Coloboma of the eye||Coloboma (sort of like a cleft) of the iris, retina, choroid, macula or disc (not the eyelid); microphthalmos (small eye) or anophthalmos (missing eye): CAUSES VISION LOSS||80%-90%|
|Choanal atresia or stenosis||The choanae are the passages that go from the back of the nose to the throat. They can be narrow (stenosis) or blocked (atresia). It can be unilateral (one-sided) or bilateral (both sides), bony or membranous.
Unilateral atresia or stenosis can be difficult to diagnose
|Cranial nerve abnormality||I – Missing or decreased sense of smell||90-100%|
|IX/X – Swallowing difficulties, aspiration||70%-90%|
|VII – Facial palsy (one side or both)||40%|
|CHARGE outer ear||Short, wide ear with little or no lobe, “snipped off” helix (outer fold), prominent antihelix (inner fold) which is discontinuous with tragus, triangular concha, decreased cartilage (floppy), often stick out, usually asymmetric .||>50%|
|CHARGE middle ear||Malformed bones of the middle ear (ossicles): CAUSES CONDUCTIVE HEARING LOSS||Common|
|CHARGE inner ear||Malformed cochlea (Mondini defect); small or absent semicircular canals: CAUSE HEARING LOSS AND BALANCE PROBLEMS .||90%|
Minor Characteristics of CHARGE: Significant, but more difficult to diagnose or less specific to CHARGE
|Heart defects||Can be any type, but many are complex, such as tetralogy of Fallot||75%|
|Cleft lip +/- cleft palate||Cleft lip with or without cleft palate, cleft palate, submucous cleft palate.||20%|
|TE fistula||Esophageal atresia, Trancheo-esophageal fistula (TEF), H-shaped TEF||15-20%|
|Kidney abnormalities||Small kidney, missing kidney, misplaced kidney, reflux||40%|
|Genital abnormalities||Males: small penis, undescended testes
Females: small labia, small or missing uterus
Both: lack of puberty without hormone intervention
|Growth deficiency||Growth hormone deficiency||15%|
|Other short stature||70%|
|Typical CHARGE Face||Square face with broad prominent forehead, arched eyebrows, large eyes, occasional ptosis (droopy lids), prominent nasal bridge with square root, thick nostrils, prominent nasal columella (between the nostrils), flat midface, small mouth, occasional small chin, larger chin with age. Facial asymmetry even without facial palsy .|
|Palm crease||Hockey-stick palmar crease.||50%|
|CHARGE Behavior||Perseverative behavior in younger individuals, obsessive compulsive behavior (OCD) in older individuals||>50%|
Other Features of CHARGE: consistent with CHARGE, possibly medically significant, but less helpful in making a diagnosis
|Chronic ear problems||Lots of infections, fluid in the ears, PE tubes until teens||85%|
|Sloping shoulders||Underdeveloped shoulder muscles, small or missing pectoral muscles, short neck.||Common|
|Limb/skeletal||Absent thumb, extra fingers, vertebral abnormalities||?|
|CNS abnormalities||Hydrocephalus, seizures, abnormalities seen on MRI or CT||Occasional|
|Thymus or parathyroid abnormality||Small or missing thymus, decreased immune system||Rare|
|Omphalocele||Omphalocele or umbilical hernia||15%|
|Nipple anomalies||Extra, missing or misplaced nipples||Occasional|
|Hypotonia||Low muscle tone –||90%|
|Scoliosis||Usually due to low muscle tone||Common|
No one feature is required to make a diagnosis of CHARGE. Every feature varies from severe to absent in different children.
What causes CHARGE syndrome?
CHARGE syndrome is a genetic condition, caused by a change (mutation) in a single gene, most often CHD7. In August, 2004, the first major gene for CHARGE syndrome was reported by a group of researchers in the Netherlands. The gene is CHD7, located on the long arm of chromosome #8. It is a regulatory gene which plays a role in turning other genes on and off. Changes (mutations) in this gene have been found in more than half of all children with CHARGE tested to date. In the vast majority, the mutation was new in the child – not detected in the parents. This confirms that CHARGE syndrome is a genetic condition caused by a new mutation in a dominant gene. Further research is needed to find other genes that can cause CHARGE and to determine the function of the CHARGE genes in the developing fetus, babies, children and adults.