What is CHARGE syndrome?
CHARGE syndrome is a congenital condition – meaning that it is present at birth. It is a rare condition which occurs in about one in every 10,000 births worldwide. CHARGE is an extremely complex syndrome that covers a pattern of birth defects. The most common problems affect the ears, eyes, nasal passages, heart, genitals, and growth; but the symptoms of the condition and its severity vary widely from person to person.
Babies with the illness are often born with life-threatening heart and/or breathing problems. Many have difficulty swallowing. Most have vision and hearing loss, and balance problems which delay their development and communication.
It is important to highlight that despite the severe medical problems they face, children with CHARGE syndrome often far exceed physical, educational and social expectations.
Why is it called CHARGE syndrome?
The name CHARGE was adopted in the early 1980s to refer to a cluster of features seen in a number of children. The letters in CHARGE stand for:
- Coloboma of the eye (part of the eye is missing because it has failed to develop properly)
- Heart defects
- Atresia of the choanae (blockage of the passages at the back of the nose)
- Retardation of growth and/or development
- Genital and/or urinary abnormalities
- Ear abnormalities and deafness
What causes CHARGE syndrome?
CHARGE syndrome is a genetic condition. Genes are units of heredity transferred from the parents to their biological children. They are stored in thread-like structures called chromosomes. Every human cell contains, in its nucleus, 23 pairs of chromosomes, and thousands of genes are encoded on each chromosome.
CHARGE is caused by a change (mutation) in a single gene called CHD7, located on chromosome #8. Studies have shown that the CHD7 gene plays a crucial role in many fetal tissues, including the eye and the inner ear.
Mutations in the CHD7 gene have been found approximately 60-65 per cent of patients with CHARGE tested. In the vast majority, the mutation was new; it was not detected in the parents and there was no history of CHARGE in the family.
In the current state of research, it seems that parents of one child with CHARGE have a maximum one to two per cent chance of having another child with the condition. Risk to children of individuals with CHARGE may be as high as 50 per cent.
What are the symptoms of CHARGE syndrome?
Major features of CHARGE syndrome
These traits are quite common in CHARGE and relatively rare in other conditions, making them particularly helpful for reaching a diagnosis. Most of them are also identifiable in a newborn.
- Coloboma: this is a ‘keyhole’-shaped defect in part of the eye, which is present at birth and doesn’t evolve. It happens where part of the eye has failed to develop properly and is missing. When present in the iris, it may limit the person’s ability to adjust to bright light. If it affects the back of the eye (retina), it will create a blank area in the person’s visual field. Sometimes the eye may be small (microphthalmia) and in rare cases, entirely absent (anophthalmia).
- Choanal atresia: this is a blockage of the passages at the back of the nose that may be caused by a membrane of skin or bone.
- Ear anomalies: the external ear may be small, with little or no lobe; or large and sticking out; and/or cup-shaped. The middle ear may have bone malformations or chronic glue ear infection. The inner ear can also be affected, leading to hearing loss, and sometimes balance problems. Hearing loss in people with CHARGE usually results from a combination of various abnormalities in the middle and inner ear.
- Facial palsy and other cranial nerve dysfunction: cranial nerve problems are very common in CHARGE. They affect mainly the first cranial nerve (causing a loss of the sense of smell); the seventh cranial nerve (which results in facial palsy); the eighth cranial nerve (leading to hearing loss and balance problems); and the ninth and tenth cranial nerves (causing swallowing problems). Children with facial palsy are more likely to have structural differences in the throat (pharynx and larynx) and difficulties swallowing.
Minor features of CHARGE syndrome
The following characteristics are all significant in establishing a final diagnosis, but they may be more difficult to spot, especially in a newborn baby. They are also less specific to CHARGE and can relate to other conditions:
- Heart defects of various kinds – from life-threatening to minor.
- Cleft lip and palate: common in children with CHARGE, cleft lip and palate are birth defects that affect the upper lip and the roof of the mouth. A cleft is a fissure, or gap.
- Genital differences: children with CHARGE often have incomplete or underdeveloped external genitals; boys are more likely to be affected. (Common problems include undescended testicles.) Both males and females with CHARGE often experience hormonal problems and difficulties with puberty.
- Kidney abnormalities: kidney is either small, misplaced, or missing.
- Growth deficiency: the child grows and develops more slowly than expected. They will need more time to reach milestones such as sitting, walking and speaking. Most adults affected by CHARGE are short.
- Characteristic facial features: these can include facial asymmetry (when the two sides of the face are different, even in the absence of facial palsy), a square face with a prominent forehead, droopy eyelids, a flat mid-face and small chin.
- Upper body hypotonia: low muscle tone, or very floppy muscles in the upper body.
Other features consistent with CHARGE syndrome
Other traits are medically significant, but not really helpful in making a diagnosis. These include:
- Chronic ear problems: infections, fluid in the ears.
- Sloping shoulders: shoulder muscles are underdeveloped; pectoral muscles are small or missing.
- Abnormally curved spine (scoliosis).
- Omphalocele: a birth defect in which the infant’s intestine or other abdominal organs stick out of the belly button.
- Umbilical hernia: soft swelling over the baby’s belly button, a symptom that the muscle through which blood vessels pass to feed the developing fetus didn’t close completely.
How is CHARGE syndrome diagnosed?
Because there is so much left to discover about CHARGE syndrome, the criteria for diagnosis are constantly under review. Even though a gene for CHARGE syndrome has been identified, the gene test is expensive and it isn’t perfect. The diagnosis of CHARGE syndrome is still clinical, meaning that it is based on the medical features seen in the patient. It is made using a combination of some of the major and minor features listed above: usually, either three major features, or two major and three minor features, are required to make a diagnosis of CHARGE.
Some babies are diagnosed as having CHARGE almost immediately. In other cases it may take years for medical professionals to put the different pieces of information together and reach a diagnosis.
What are the treatments for CHARGE syndrome?
Each CHARGE patient presents a unique range of medical problems that affect them more or less severely, and that will dictate which treatments may help them. Because of the complexity of their condition, these patients need to be followed by a team of many specialists working together: ENT (ear, nose and throat) doctor, cardiologist, gynecologist, endocrinologist, ophthalmologist, orthodontist – amongst others.
Babies with CHARGE syndrome will require medical and educational intervention for many years. They are likely to spend many months in hospital having extensive surgery and other treatments.
Surgery may be necessary immediately after birth in case of choanal atresia, to unblock of the passages at the back of the nose.
Heart defects sometimes resolve themselves over time, but often emergency surgery is needed soon after a child is born.
A cleft lip can be surgically repaired when a baby is about four months old. A cleft palate is usually operated on when the child is one year old.
Various medical treatments, therapies, and surgeries can help with facial palsy.
Many young people with CHARGE will not go through puberty without the support of hormone treatment. Failure to adequately replace sex hormones in puberty may also lead to brittle bones (osteoporosis) in adult life.
Last reviewed: 16-02-2020 || Next review due: 16-02-2023