Rare Gastroenterology News

Disease Profile

CHARGE syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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;

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]

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.

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
Hypogonadotropic 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
Blockage of the rear opening of the nasal cavity
Obstruction 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
Mental retardation, nonspecific
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

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]

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.

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

    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.

      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

        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

          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.

            References

            1. CHARGE syndrome. Genetics Home Reference. February 2017; https://ghr.nlm.nih.gov/condition/charge-syndrome.
            2. Signs and Symptoms. The CHARGE Syndrome Foundation. https://www.chargesyndrome.org/about-charge/signs-symptoms/. Accessed 2/16/2017.
            3. Seema R Lalani, Margaret A Hefner, John W Belmont, and Sandra LH Davenport. CHARGE syndrome. GeneReviews. February 2, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1117/.
            4. 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.
            5. CHARGE syndrome. Genetics Home Reference. May 2008; https://ghr.nlm.nih.gov/condition/charge-syndrome. Accessed 3/8/2013.

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