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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Anosmia	Lost smell	0000458
Aplasia/Hypoplasia of the earlobes	Absent/small ear lobes Absent/underdeveloped ear lobes [ more ]	0009906
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Delayed puberty	Delayed pubertal development Delayed pubertal growth Pubertal delay [ more ]	0000823
External ear malformation		0008572
Feeding difficulties in infancy		0008872
Global developmental delay		0001263
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Hypogonadotrophic hypogonadism		0000044
Hypoplasia of the semicircular canal		0011382
Iris coloboma	Cat eye	0000612
Micropenis	Short penis Small penis [ more ]	0000054
Overfolded helix	Overfolded ears	0000396
30%-79% of people have these symptoms
Abnormal aortic valve morphology		0001646
Abnormal cardiac septum morphology		0001671
Abnormal morphology of female internal genitalia		0000008
Abnormal soft palate morphology		0100736
Anophthalmia	Absence of eyeballs Failure of development of eyeball Missing eyeball No eyeball [ more ]	0000528
Anterior hypopituitarism		0000830
Aortic arch aneurysm		0005113
Attention deficit hyperactivity disorder	Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ]	0007018
Autism		0000717
Bifid scrotum	Cleft of scrotum	0000048
Choanal atresia	Obstruction of the rear opening of the nasal cavity Blockage of the rear opening of the nasal cavity [ more ]	0000453
Chorioretinal coloboma	Birth defect that causes a hole in the innermost layer at the back of the eye	0000567
Cleft palate	Cleft roof of mouth	0000175
Cleft upper lip	Harelip	0000204
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Dimple chin	Chin butt Chin dent Chin dimple Chin skin dimple Indentation of chin [ more ]	0010751
Facial asymmetry	Asymmetry of face Unsymmetrical face Crooked face [ more ]	0000324
Facial palsy	Bell's palsy	0010628
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Intellectual disability	Mental deficiency Mental retardation, nonspecific Mental retardation Mental-retardation [ more ]	0001249
Interrupted aortic arch		0011611
Labial hypoplasia	Underdeveloped labia	0000066
Low-set, posteriorly rotated ears		0000368
Microphthalmia	Abnormally small eyeball	0000568
Muscular hypotonia	Low or weak muscle tone	0001252
Narrow face	Decreased breadth of face Decreased width of face [ more ]	0000275
Narrow mouth	Small mouth	0000160
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Obsessive-compulsive behavior	Obsessive compulsive behavior	0000722
Optic atrophy		0000648
Patent ductus arteriosus		0001643
Polyhydramnios	High levels of amniotic fluid	0001561
Postnatal growth retardation	Growth delay as children	0008897
Ptosis	Drooping upper eyelid	0000508
Short stature	Decreased body height Small stature [ more ]	0004322
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Tetralogy of Fallot		0001636
5%-29% of people have these symptoms
Abnormality of bone mineral density		0004348
Abnormality of immune system physiology		0010978
Abnormality of the adrenal glands	Adrenal abnormalities	0000834
Abnormality of the ribs	Rib abnormalities	0000772
Abnormality of tibia morphology	Abnormality of the shankbone Abnormality of the shinbone [ more ]	0002992
Abnormality of vision	Abnormality of sight Vision issue [ more ]	0000504
Absent radius	Missing outer large bone of forearm	0003974
Aplasia/Hypoplasia of the cerebellum	Absent/small cerebellum Absent/underdeveloped cerebellum [ more ]	0007360
Aqueductal stenosis		0002410
Bifid femur	Split thighbone Notched thighbone [ more ]	0010443
Brachydactyly	Short fingers or toes	0001156
Clinodactyly of the 5th finger	Permanent curving of the pinkie finger	0004209
Dandy-Walker malformation		0001305
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Eyelid coloboma	Cleft eyelid Notched eyelid [ more ]	0000625
Hand monodactyly		0004058
Hemivertebrae	Missing part of vertebrae	0002937
Highly arched eyebrow	Arched eyebrows Broad, arched eyebrows High, rounded eyebrows High-arched eyebrows Thick, flared eyebrows [ more ]	0002553
Holoprosencephaly		0001360
Horseshoe kidney	Horseshoe kidneys	0000085
Hydronephrosis		0000126
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypoplasia of the ulna	Underdeveloped inner large forearm bone	0003022
Hypoplasia of the zygomatic bone	Cheekbone underdevelopment Decreased size of cheekbone Underdevelopment of cheekbone [ more ]	0010669
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Lacrimation abnormality	Abnormality of tear production	0000632
Laryngomalacia	Softening of voice box tissue	0001601
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Microtia	Small ears Underdeveloped ears [ more ]	0008551
Preauricular skin tag		0000384
Respiratory insufficiency	Respiratory impairment	0002093
Scoliosis		0002650
Talipes		0001883
Tracheoesophageal fistula		0002575
Vesicoureteral reflux		0000076
1%-4% of people have these symptoms
Arrhinencephaly		0002139
Percent of people who have these symptoms is not available through HPO
Abnormal palmar dermatoglyphics		0001018
Anal atresia	Absent anus	0002023
Anal stenosis	Narrowing of anal opening	0002025
Aplasia/Hypoplasia of the thymus	Absent/small thymus Absent/underdeveloped thymus [ more ]	0010515
Atrial septal defect	An opening in the wall separating the top two chambers of the heart Hole in heart wall separating two upper heart chambers [ more ]	0001631
Autosomal dominant inheritance		0000006
Cupped ear	Cup-shaped ears Simple, cup-shaped ears [ more ]	0000378
Double outlet right ventricle		0001719
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Down-sloping shoulders	Rounded shoulders Rounded, sloping shoulders Sloping shoulders [ more ]	0200021
Duodenal atresia	Absence or narrowing of first part of small bowel	0002247
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Esophageal atresia	Birth defect in which part of esophagus did not develop	0002032
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Gonadotropin deficiency		0008213
Growth hormone deficiency		0000824
Hand polydactyly	Extra finger	0001161
Hypocalcemia	Low blood calcium levels	0002901
Hypothyroidism	Underactive thyroid	0000821
Lop ear		0000394
Lymphopenia	Decreased blood lymphocyte number Low lymphocyte number [ more ]	0001888
Malar flattening	Zygomatic flattening	0000272
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Mixed hearing impairment	Hearing loss, mixed Mixed hearing loss [ more ]	0000410
Omphalocele		0001539
Parathyroid hypoplasia	Small parathyroid glands Underdeveloped parathyroid glands [ more ]	0000860
Posterior choanal atresia		0004496
Pulmonic stenosis	Narrowing of pulmonic valve	0001642
Renal agenesis	Absent kidney Missing kidney [ more ]	0000104
Renal hypoplasia	Small kidneys Underdeveloped kidneys [ more ]	0000089
Retinal coloboma	Hole in the back of the eye	0000480
Short thumb	Short thumbs Small thumbs [ more ]	0009778
Sporadic	No previous family history	0003745
Square face	Square facial shape	0000321
Umbilical hernia		0001537
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Webbed neck	Neck webbing	0000465

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 3/1/2020

Do you have updated information on this disease? We want to hear from you.

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

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.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes Abruzzo-Erickson syndrome, Kallmann syndrome, 22q11.2 deletion syndrome, VACTERL/VATER association, Kabuki syndrome, renal coloboma syndrome, Cat-eye syndrome, Joubert syndrome, BOR syndrome, 5q11.2 microdeletion syndrome (see these terms) and other chromosomal microdeletion syndromes. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with CHARGE syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for CHARGE syndrome:
United States Immunodeficiency Network (USIDENT) Registry

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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

About Face International
51 Wolseley Street
Toronto, ON M5T 1A4
Canada
Toll-free: 1-800-665-3223
Telephone: +1-416-597-2229
Fax: +1-416-597-8494
E-mail: info@aboutface.ca
Website: https://www.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: 1-800-535-3643
Telephone: +1-214-570-9099
Fax: +1-214-570-8811
E-mail: contactCCA@ccakids.com
Website: https://ccakids.org/

Do you know of an organization? We want to hear from you.

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

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.
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.

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.