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Genetics Home Reference: your guide to understanding genetic conditions
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CHARGE syndrome

Reviewed May 2008

What is CHARGE syndrome?

CHARGE syndrome is a disorder that affects many areas of the body. CHARGE stands for coloboma, heart defect, atresia choanae (also known as choanal atresia), retarded growth and development, genital abnormality, and ear abnormality. The pattern of malformations varies among individuals with this disorder, and infants often have multiple life-threatening medical conditions. The diagnosis of CHARGE syndrome is based on a combination of major and minor characteristics.

The major characteristics of CHARGE syndrome are more specific to this disorder than are the minor characteristics. Many individuals with CHARGE syndrome have a hole in one of the structures of the eye (coloboma), which forms during early development. A coloboma may be present in one or both eyes and can affect a person's vision, depending on its size and location. Some people also have small eyes (microphthalmia). One or both nasal passages may be narrowed (choanal stenosis) or completely blocked (choanal atresia). Individuals with CHARGE syndrome frequently have cranial nerve abnormalities. The cranial nerves emerge directly from the brain and extend to various areas of the head and neck, controlling muscle movement and transmitting sensory information. Abnormal function of certain cranial nerves can cause swallowing problems, facial paralysis, a sense of smell that is diminished (hyposmia) or completely absent (anosmia), and mild to profound hearing loss. People with CHARGE syndrome also typically have middle and inner ear abnormalities and unusually shaped ears.

The minor characteristics of CHARGE syndrome are not specific to this disorder; they are frequently present in people without CHARGE syndrome. The minor characteristics include heart defects, slow growth starting in late infancy, developmental delay, and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Individuals frequently have hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Males are often born with an unusually small penis (micropenis) and undescended testes (cryptorchidism). External genitalia abnormalities are seen less often in females with CHARGE syndrome. Puberty can be incomplete or delayed. Individuals may have a tracheoesophageal fistula, which is an abnormal connection (fistula) between the esophagus and the trachea. People with CHARGE syndrome also have distinctive facial features, including a square-shaped face and difference in the appearance between the right and left sides of the face (facial asymmetry). Individuals have a wide range of cognitive function, from normal intelligence to major learning disabilities with absent speech and poor communication.

How common is CHARGE syndrome?

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

What genes are related to CHARGE syndrome?

Mutations in the CHD7 gene cause more than half of all cases of CHARGE syndrome. The CHD7 gene provides instructions for making a protein that most likely regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.

Most mutations in the CHD7 gene lead to the production of an abnormally short, nonfunctional CHD7 protein, which presumably disrupts chromatin remodeling and the regulation of gene expression. Changes in gene expression during embryonic development likely cause the signs and symptoms of CHARGE syndrome.

About one-third of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. Researchers suspect that other genetic and environmental factors may be involved in these individuals.

Related Gene(s)

Changes in this gene are associated with CHARGE syndrome.

  • CHD7

How do people inherit CHARGE syndrome?

CHARGE syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the CHD7 gene and occur in people with no history of the disorder in their family. In rare cases, an affected person inherits the mutation from an affected parent.

Where can I find information about diagnosis or management of CHARGE syndrome?

These resources address the diagnosis or management of CHARGE syndrome and may include treatment providers.

  • Gene Review: CHARGE Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1117)
  • Genetic Testing Registry: CHARGE association (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265354)
  • MedlinePlus Encyclopedia: Choanal atresia (http://www.nlm.nih.gov/medlineplus/ency/article/001642.htm)
  • MedlinePlus Encyclopedia: Coloboma (http://www.nlm.nih.gov/medlineplus/ency/article/003318.htm)
  • MedlinePlus Encyclopedia: Facial Paralysis (http://www.nlm.nih.gov/medlineplus/ency/article/003028.htm)

You might also find information on the diagnosis or management of CHARGE syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/charge-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/charge-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about CHARGE syndrome?

You may find the following resources about CHARGE syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for CHARGE syndrome?

  • CHARGE acronym (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness)
  • CHARGE association
  • Hall-Hittner syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about CHARGE syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding CHARGE syndrome?

anosmia ; atresia ; autosomal ; autosomal dominant ; cell ; chromatin ; chromatin remodeling ; cleft palate ; cranial nerves ; cryptorchidism ; developmental delay ; diagnosis ; disabilities ; DNA ; embryonic ; esophagus ; fistula ; gene ; gene expression ; genitalia ; hypogonadism ; hypogonadotropic ; hypoplasia ; inherited ; micropenis ; mutation ; palate ; protein ; puberty ; stenosis ; syndrome ; testes

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Blake KD, Prasad C. CHARGE syndrome. Orphanet J Rare Dis. 2006 Sep 7;1:34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16959034?dopt=Abstract)
  • Gene Review: CHARGE Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1117)
  • Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet. 2006 Feb;78(2):303-14. Epub 2005 Dec 29. (http://www.ncbi.nlm.nih.gov/pubmed/16400610?dopt=Abstract)
  • Sanlaville D, Etchevers HC, Gonzales M, Martinovic J, Clément-Ziza M, Delezoide AL, Aubry MC, Pelet A, Chemouny S, Cruaud C, Audollent S, Esculpavit C, Goudefroye G, Ozilou C, Fredouille C, Joye N, Morichon-Delvallez N, Dumez Y, Weissenbach J, Munnich A, Amiel J, Encha-Razavi F, Lyonnet S, Vekemans M, Attié-Bitach T. Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet. 2006 Mar;43(3):211-217. Epub 2005 Sep 16. (http://www.ncbi.nlm.nih.gov/pubmed/16169932?dopt=Abstract)
  • Sanlaville D, Verloes A. CHARGE syndrome: an update. Eur J Hum Genet. 2007 Apr;15(4):389-99. Epub 2007 Feb 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17299439?dopt=Abstract)
  • Verloes A. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. 2005 Mar 15;133A(3):306-8. (http://www.ncbi.nlm.nih.gov/pubmed/15666308?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2008
Published: December 22, 2014