CHARGE Syndrome: A Genetic Disease with Many Features

CHARGE Syndrome - How to Make Sense of This Complex Medical Disease

child with CHARGE syndrome
What is CHARGE syndrome and what types of abnormalities are included in the diagnosis?. Credit: www.chargeacrosseurope.com / Google Images

What is CHARGE Syndrome?

In 1981, the term CHARGE was created to describe clusters of birth defects that had been recognized in children. CHARGE stands for:

  • Coloboma (eye)
  • Heart defects of any type
  • Atresia (choanal)
  • Retardation (of growth and/or development)
  • Genital anomaly
  • Ear anomaly

It was recommended that diagnosis of the syndrome be based on the presence of four of these physical features. Since then, physicians have recognized that this definition and rule for diagnosis do not take into account many other physical characteristics of CHARGE syndrome, or the fact that some children with the syndrome did not meet the criteria for diagnosis.

Genetics of CHARGE Syndrome

A gene associated with CHARGE syndrome has been identified on chromosome 8 and involves mutations of the CHD7 gene (the CHD7 gene is the only gene currently felt to be involved with the syndrome.) Although it is now known that CHARGE syndrome is a complex medical syndrome caused by a genetic defect, the name has not changed. Though CHD7 gene mutations are inherited in an autosomal dominant fashion, most cases come about from a new mutation and the infant is usually the only child in the family with the syndrome.

Incidence of CHARGE Syndrome

CHARGE syndrome occurs in approximately 1 in 8,500 to 10,000 births worldwide.

Symptoms of CHARGE Syndrome

The physical attributes of a child with CHARGE syndrome ranges from near normal to severe. Each child born with the syndrome may have different physical problems and some of the most common features or birth defects are:

C—Coloboma of the Eye:

  • This ailment affects about 80 to 90 percent of people diagnosed with CHARGE syndrome
  • A coloboma consists of a fissure (crack) usually in the back of the eye
  • One or both eyes may also be too small (microphthalmos) or missing (anophthalmos)

C may also refer to a Cranial Nerve Abnormality: 

  • 90 to 100 percent of people with CHARGE syndrome have a decrease or complete loss of their sense of smell (anosmia)
  • 70 to 80 percent of people have difficulty swallowing. 
  • Facial paralysis (palsy) on one or both sides occurs in 50 to 90 percent of people with the syndrome

H—Heart Defect: 

  • 75 percent of individuals are affected by different types of heart defects
  • The most frequent heart defect is a hole in the heart (atrial septal defect)

A—Atresia of the Choanae: 

  • An atresia refers to the absence of narrowing of a passage in the body. In people with CHARGE syndrome, the back of the nasal sinuses on one or both sides is narrowed (stenosis) or doesn't connect with the back of the throat (atresia)
  • This atresia is present in 35 to 65 percent of individuals with CHARGE syndrome

R—Retardation (Mental and Growth)

  • 70 percent of individuals affected by CHARGE have decreased IQs which may range from nearly normal to severe mental retardation
  • 80 percent of individuals are affected by growth retardation, and this growth retardation is usually detected in the first six months of life when the infant fails to grow normally
  • Growth retardation is due to growth hormone deficiencies and/or feeding difficulty (the child’s growth tends to catch up after infancy)

G—Genital Underdevelopment: 

  • Underdeveloped genitals are a telltale sign of CHARGE syndrome in males, but not so much in females
  • 80 to 90 percent of males are affected by genital underdevelopment, but only 15 to 25 percent of females with the syndrome are affected

E—Ear Abnormalities:

  • Ear abnormalities affect 95 to 100 percent of individuals have deformities of the outer ear which can be visualized
  •  60 to 90 percent of people also experience problems in the inner ear, such as abnormal semicircular canals or nerve defects which may result in deafness

There are many other physical problems a child with CHARGE syndrome may have in addition to these more common symptoms listed above.

How a Child Is Diagnosed With CHARGE Syndrome

The diagnosis of CHARGE syndrome is based on the cluster of physical symptoms and attributes displayed by each child.

The three most telling symptoms are the 3 C’s: Coloboma, Choanal atresia, and abnormal semicircular Canals in the ears.

There are other major symptoms, such as the abnormal appearance of the ears, that are common in CHARGE syndrome patients but less common in other conditions. Some symptoms, such as a heart defect, may also occur in other syndromes or conditions, and thus may be less helpful in confirming a diagnosis.

An infant suspected of having CHARGE syndrome should be evaluated by a medical geneticist who is familiar with the syndrome. Genetic testing can be done, but it is expensive and only performed by certain laboratories.

How CHARGE Syndrome Is Treated

Infants born with CHARGE syndrome have many medical and physical problems, some of which, such as a heart defect, may be life-threatening. A number of different types of medical and/or surgical treatments may be needed to treat such a defect.

Physical, occupational, and speech therapy can help a child reach his/her developmental potential. Most children with CHARGE syndrome will need special education because of the developmental and communication delays caused by hearing and vision loss.

Quality of Life for People with CHARGE Syndrome

Since the symptoms any one person with CHARGE syndrome can vary tremendously, it is hard to talk about what life is like for they "typical" person with the syndrome. One study looked at over 50 people living with the disease who were between the ages of 13 and 39. Overall, the average intellectual level among these people was at a 4th grade academic level. The most frequent issues faced included bone health issues, sleep apnea, retinal detachments, anxiety, and aggression. Unfortunately, the sensory issues can interfere with relationships with friends outside of the family, but therapy, whether speech, physical, or occupational can be very helpful. It's helpful for family and friends, especially to be aware of these sensory issues, as hearing problems have been mistaken as metal retardation for centuries.

Sources:

Hartshorne, N., Hudson, A., MacCuspie, J. et al. Quality of Life in Adolescents and Adults with CHARGE Syndrome. American Journal of Medical Genetics. Part A. 2016. 170(8):2012-21.

Hudson, A., Trider, C., and K. Blake. CHARGE Syndrome. Pediatrics in Review. 2017. 38(1):56-59.

Vesseur, A., Langereis, M., Free, R. et al. Influence of Hearing Loss and Cognitive Abilities on Language Development in CHARGE Syndrome. American Journal of Medical Genetics. Part A. 2016. 170(8):2022-30.

U.S. National Library of Medicine. Genetics Home Reference. CHARGE Syndrome. Updated 01/03/17. https://ghr.nlm.nih.gov/condition/charge-syndrome#statistics

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