CHARGE syndrome

Title

Other Names:

Coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies; CHARGE association; Hall-Hittner syndrome

Categories:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases; Eye diseases; Female Reproductive Diseases; Heart Diseases; Immune System Diseases; Kidney and Urinary Diseases; Male Reproductive Diseases; Mouth Diseases See More

Summary Summary

CHARGE syndrome is a congenital condition (present from birth) that affects many areas of the body. CHARGE stands for coloboma, heart defect, atresia choanae (also known as choanal atresia), restricted growth and development, genital abnormality, and ear abnormality.^[1] Signs and symptoms vary among people with this condition; however, infants often have multiple life-threatening medical conditions.^[2] The diagnosis of CHARGE syndrome is based on a combination of major and minor characteristics. In more than half of all cases, mutations in the CHD7 gene cause CHARGE syndrome. When caused by a mutation in the CHD7 gene, it can be inherited in an autosomal dominant pattern; although most cases result from new (de novo) mutations in the gene and occur in people with no history of the condition in their family. Although there is no specific treatment or cure, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options for each person.^[1]^[3]

Last updated: 2/16/2017

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the inner ear	Very frequent (present in 80%-99% of cases)
Aplasia/Hypoplasia of the earlobes	Very frequent (present in 80%-99% of cases)
Cryptorchidism	Very frequent (present in 80%-99% of cases)
External ear malformation	Very frequent (present in 80%-99% of cases)
Facial palsy	Very frequent (present in 80%-99% of cases)
Hearing impairment	Very frequent (present in 80%-99% of cases)
Hypoplasia of penis	Very frequent (present in 80%-99% of cases)
Iris coloboma	Very frequent (present in 80%-99% of cases)
Overfolded helix	Very frequent (present in 80%-99% of cases)
Abnormality of female internal genitalia	Frequent (present in 30%-79% of cases)
Abnormality of the aortic valve	Frequent (present in 30%-79% of cases)
Abnormality of the cardiac septa	Frequent (present in 30%-79% of cases)
Abnormality of the soft palate	Frequent (present in 30%-79% of cases)
Anophthalmia	Frequent (present in 30%-79% of cases)
Anosmia	Frequent (present in 30%-79% of cases)
Anterior hypopituitarism	Frequent (present in 30%-79% of cases)
Attention deficit hyperactivity disorder	Frequent (present in 30%-79% of cases)
Autism	Frequent (present in 30%-79% of cases)
Bifid scrotum	Frequent (present in 30%-79% of cases)
Chin dimple	Frequent (present in 30%-79% of cases)
Choanal atresia	Frequent (present in 30%-79% of cases)
Chorioretinal coloboma	Frequent (present in 30%-79% of cases)
Cleft palate	Frequent (present in 30%-79% of cases)
Cleft upper lip	Frequent (present in 30%-79% of cases)
Delayed eruption of teeth	Frequent (present in 30%-79% of cases)
Dilatation of the aortic arch	Frequent (present in 30%-79% of cases)
Facial asymmetry	Frequent (present in 30%-79% of cases)
Gastroesophageal reflux	Frequent (present in 30%-79% of cases)
Hypogonadotrophic hypogonadism	Frequent (present in 30%-79% of cases)
Intellectual disability	Frequent (present in 30%-79% of cases)
Interrupted aortic arch	Frequent (present in 30%-79% of cases)
Labial hypoplasia	Frequent (present in 30%-79% of cases)
Low-set, posteriorly rotated ears	Frequent (present in 30%-79% of cases)
Microphthalmia	Frequent (present in 30%-79% of cases)
Muscular hypotonia	Frequent (present in 30%-79% of cases)
Narrow face	Frequent (present in 30%-79% of cases)
Narrow mouth	Frequent (present in 30%-79% of cases)
Nystagmus	Frequent (present in 30%-79% of cases)
Obsessive-compulsive behavior	Frequent (present in 30%-79% of cases)
Optic atrophy	Frequent (present in 30%-79% of cases)
Patent ductus arteriosus	Frequent (present in 30%-79% of cases)
Polyhydramnios	Frequent (present in 30%-79% of cases)
Ptosis	Frequent (present in 30%-79% of cases)
Strabismus	Frequent (present in 30%-79% of cases)
Tetralogy of Fallot	Frequent (present in 30%-79% of cases)
Abnormality of bone mineral density	Occasional (present in 5%-29% of cases)
Abnormality of immune system physiology	Occasional (present in 5%-29% of cases)
Abnormality of the adrenal glands	Occasional (present in 5%-29% of cases)
Abnormality of the ribs	Occasional (present in 5%-29% of cases)
Abnormality of the tibia	Occasional (present in 5%-29% of cases)
Abnormality of vision	Occasional (present in 5%-29% of cases)
Absent radius	Occasional (present in 5%-29% of cases)
Aplasia/Hypoplasia of the cerebellum	Occasional (present in 5%-29% of cases)
Aqueductal stenosis	Occasional (present in 5%-29% of cases)
Bifid femur	Occasional (present in 5%-29% of cases)
Brachydactyly syndrome	Occasional (present in 5%-29% of cases)
Cleft eyelid	Occasional (present in 5%-29% of cases)
Clinodactyly of the 5th finger	Occasional (present in 5%-29% of cases)
Dandy-Walker malformation	Occasional (present in 5%-29% of cases)
Epicanthus	Occasional (present in 5%-29% of cases)
Feeding difficulties in infancy	Occasional (present in 5%-29% of cases)
Hand monodactyly	Occasional (present in 5%-29% of cases)
Hemivertebrae	Occasional (present in 5%-29% of cases)
Highly arched eyebrow	Occasional (present in 5%-29% of cases)
Holoprosencephaly	Occasional (present in 5%-29% of cases)
Horseshoe kidney	Occasional (present in 5%-29% of cases)
Hydronephrosis	Occasional (present in 5%-29% of cases)
Hypertelorism	Occasional (present in 5%-29% of cases)
Hypoplasia of the ulna	Occasional (present in 5%-29% of cases)
Hypoplasia of the zygomatic bone	Occasional (present in 5%-29% of cases)
Intrauterine growth retardation	Occasional (present in 5%-29% of cases)
Lacrimation abnormality	Occasional (present in 5%-29% of cases)
Laryngomalacia	Occasional (present in 5%-29% of cases)
Microcephaly	Occasional (present in 5%-29% of cases)
Microtia	Occasional (present in 5%-29% of cases)
Preauricular skin tag	Occasional (present in 5%-29% of cases)
Respiratory insufficiency	Occasional (present in 5%-29% of cases)
Scoliosis	Occasional (present in 5%-29% of cases)
Talipes	Occasional (present in 5%-29% of cases)
Tracheoesophageal fistula	Occasional (present in 5%-29% of cases)
Vesicoureteral reflux	Occasional (present in 5%-29% of cases)
Abnormal palmar dermatoglyphics	Very rare (present in 1%-4% of cases)
Abnormality of the nipple	Very rare (present in 1%-4% of cases)
Anal atresia	Very rare (present in 1%-4% of cases)
Anal stenosis	Very rare (present in 1%-4% of cases)
Arrhinencephaly	Very rare (present in 1%-4% of cases)
Cupped ear	Very rare (present in 1%-4% of cases)
Down-sloping shoulders	Very rare (present in 1%-4% of cases)
Growth hormone deficiency	Very rare (present in 1%-4% of cases)
Hand polydactyly	Very rare (present in 1%-4% of cases)
Lop ear	Very rare (present in 1%-4% of cases)
Micrognathia	Very rare (present in 1%-4% of cases)
Mixed hearing impairment	Very rare (present in 1%-4% of cases)
Omphalocele	Very rare (present in 1%-4% of cases)
Renal agenesis	Very rare (present in 1%-4% of cases)
Renal hypoplasia	Very rare (present in 1%-4% of cases)
Retinal coloboma	Very rare (present in 1%-4% of cases)
Short thumb	Very rare (present in 1%-4% of cases)
Split hand	Very rare (present in 1%-4% of cases)
Webbed neck	Very rare (present in 1%-4% of cases)
Aplasia/Hypoplasia of the thymus	-
Atrial septal defect	-
Autosomal dominant inheritance	-
Coloboma	-
Delayed puberty	-
Double outlet right ventricle	-
Downslanted palpebral fissures	-
Duodenal atresia	-
Dysphagia	-
Esophageal atresia	-
Feeding difficulties	-
Gonadotropin deficiency	-
Hypocalcemia	-
Hypothyroidism	-
Lymphopenia	-
Malar flattening	-
Micropenis	-
Parathyroid hypoplasia	-
Phenotypic variability	-
Posterior choanal atresia	-
Postnatal growth retardation	-
Pulmonic stenosis	-
Sporadic	-
Square face	-
Umbilical hernia	-
Ventricular septal defect	-

Last updated: 5/8/2017

Cause Cause

CHARGE syndrome is caused by mutations in the CHD7 gene in the majority of cases. Almost all mutations in affected individuals are de novo, which means they occur for the first time as new mutations and are not inherited from a parent. However, autosomal dominant inheritance with transmission from parent to child has been reported in rare cases.^[3]^[4]^[5]

The CHD7 gene provides instructions for making a protein that most likely regulates gene activity (expression). Most mutations in the CHD7 gene lead to the production of an abnormally short, nonfunctional CHD7 protein, which is thought to disrupt 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. The cause is unknown in these individuals, but researchers suspect that other genetic and/or environmental factors may be involved.^[5]

Last updated: 3/8/2013

Inheritance Inheritance

CHARGE syndrome is usually not inherited, typically occurring due to a new (de novo) gene mutation in the affected individual. However, rare familial cases inherited in an autosomal dominant manner have been described.

To our knowledge, all individuals who have a CHD7 mutation have some features of CHARGE syndrome (i.e. penetrance is 100%). In rare instances, one parent may have mild features, and the family history may appear to be negative because of failure to recognize the mild features of the condition.

The risk to the siblings of an affected individual depends on the genetic status of the individual's parents. If a parent of an affected child also has CHARGE syndrome, the risk for each sibling to inherit the condition is 50%. If neither parent is affected, the risk to each sibling of an affected child is estimated to be 1%-2%, most likely attributable to germline mosaicism. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing CHD7 mutation has been identified in an affected family member.^[3]

Last updated: 3/11/2013

Diagnosis Diagnosis

Genetic testing is available for CHARGE syndrome. The CHD7 gene is the only gene in which mutations are known to cause CHARGE syndrome. The CHD7 mutation detection rate when sequence analysis is performed is estimated to be 65%-70% for all typical and suspected cases combined.^[3]

GeneTests lists the names of laboratories that are performing clinical genetic testing for CHARGE syndrome. To view the contact information for these laboratories, click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families. Therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

Last updated: 3/11/2013

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Do you have updated information on this condition? Let us know.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

AboutFace International
123 Edward Street Suite 1003
Toronto ON M5G 1E2
Canada
Toll-free: 800-665-3223
Telephone: 416-597-2229
Fax: 416-597-8494
E-mail: info@aboutfaceinternational.org
Website: http://aboutface.ca/
CHARGE Syndrome Foundation
141 Middle Neck Road
Sands Point, NY 11050
Telephone: 800-442-7604; 516-684-4720
Fax: 516-883-9060
E-mail: info@chargesyndrome.org
Website: http://www.chargesyndrome.org
Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas, TX 75240
Toll-free: 800-535-3643
Telephone: 214-570-9099
Fax: 214-570-8811
E-mail: contactCCA@ccakids.com
Website: http://www.ccakids.com/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The CHARGE Syndrome Foundation offers information on CHARGE syndrome
Genetics Home Reference (GHR) contains information on CHARGE syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss CHARGE syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

NCATS Co-Sponsored Conferences

Fifth International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion Thursday, May 28, 2009 - Saturday, May 30, 2009
Location: Hilton Anatole, Dallas, TX
Description: The main objective of this conference was to focus on the current problems associated with pediatric cardiac patients during and after acute or chronic cardiac support. At this conference, we brought together many distinguished physicians and scientists to define precisely the current problems and to suggest solutions with novel approaches.

Contact: Dr. Frank Evans, NHLBI301-402-2647

Co-funding Institute(s): National Heart, Lung, and Blood Institute
- Agenda ( - 708KB)
- Proceedings ( - 2908KB)
- Speakers ( - 85KB)
- Summary ( - 62KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have a son with CHARGE syndrome and would like to know if he inherited it from a parent or if it's random. Are we carriers of the syndrome, and could it happen again? Can any of my healthy kids also be a carrier causing one of them to have children with the syndrome? See answer

Have a question? Contact a GARD Information Specialist.

References References

CHARGE syndrome. Genetics Home Reference. February 2017; http://ghr.nlm.nih.gov/condition/charge-syndrome.
Signs and Symptoms. The CHARGE Syndrome Foundation. https://www.chargesyndrome.org/about-charge/signs-symptoms/. Accessed 2/16/2017.
Seema R Lalani, Margaret A Hefner, John W Belmont, and Sandra LH Davenport. CHARGE syndrome. GeneReviews. February 2, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1117/.
Bergman JE, Janssen N, Hoefsloot LH, Jongmans MC, Hofstra RM, van Ravenswaaij-Arts CM. CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype. J Med Genet. May 2011; 48(5):334-342.
CHARGE syndrome. Genetics Home Reference. May 2008; http://ghr.nlm.nih.gov/condition/charge-syndrome. Accessed 3/8/2013.