What are the other Names for this Condition? (Also known as/Synonyms)

• CHARGE Association
• Hall-Hittner Syndrome

What is CHARGE Syndrome? (Definition/Background Information)

• 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
• Signs and symptoms vary among people with this condition; however, infants often have multiple life-threatening medical conditions 
• 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

(Source: CHARGE Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets CHARGE Syndrome? (Age and Sex Distribution)

• CHARGE Syndrome is a rare, congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for CHARGE Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since CHARGE Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of CHARGE Syndrome? (Etiology)

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
• 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.

• 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

(Source: CHARGE Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of CHARGE Syndrome?

The signs and symptoms of CHARGE Syndrome vary, but may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of the inner ear
• Aplasia/hypoplasia of the earlobes
• Cryptorchidism
• External ear malformation
• Facial palsy
• Hearing impairment
• Hypoplasia of penis
• Iris coloboma
• Overfolded helix

Frequently present symptoms in 30-79% of the cases:

• Abnormality of female internal genitalia
• Abnormality of the aortic valve
• Abnormality of the cardiac septa
• Abnormality of the soft palate
• Anophthalmia
• Anosmia
• Anterior hypopituitarism
• Attention deficit hyperactivity disorder
• Autism
• Bifid scrotum
• Choanal atresia
• Chorioretinal coloboma
• Cleft upper lip
• Delayed eruption of teeth
• Dilatation of the aortic arch
• Dimple chin
• Facial asymmetry
• Gastroesophageal reflux
• Hypogonadotropic hypogonadism
• Intellectual disability
• Interrupted aortic arch
• Labial hypoplasia
• Low-set, posteriorly rotated ears
• Microphthalmia
• Muscular hypotonia
• Narrow face
• Narrow mouth
• Nystagmus
• Obsessive-compulsive behavior
• Optic atrophy
• Patent ductus arteriosus
• Polyhydramnios
• Ptosis
• Strabismus
• Tetralogy of Fallot

Less frequently present symptoms in 5-29% of the cases:

• Abnormality of bone mineral density
• Abnormality of immune system physiology
• Abnormality of the adrenal glands
• Abnormality of the ribs
• Abnormality of tibia morphology
• Abnormality of vision
• Absent radius
• Aplasia/Hypoplasia of the cerebellum
• Aqueductal stenosis
• Bifid femur
• Brachydactyly
• Cleft eyelid
• Clinodactyly of the 5th finger
• Dandy-Walker malformation
• Epicanthus
• Feeding difficulties in infancy
• Hand monodactyly
• Hemivertebrae
• Highly arched eyebrow
• Holoprosencephaly
• Horseshoe kidney
• Hydronephrosis
• Hypertelorism
• Hypoplasia of the ulna
• Hypoplasia of the zygomatic bone
• Intrauterine growth retardation
• Lacrimation abnormality 
• Laryngomalacia
• Microcephaly
• Microtia
• Respiratory insufficiency
• Scoliosis
• Talipes
• Vesicoureteral reflux
• Tracheoesophageal fistula

(Source: CHARGE Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is CHARGE Syndrome Diagnosed?

• 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
• Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing CHD7 mutation has been identified in an affected family member

(Source: CHARGE Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of CHARGE Syndrome?

The complications of CHARGE Syndrome may include:

• Immobility due to bone and joint abnormalities
• Curved spine
• Severe involvement of certain vital organs

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is CHARGE Syndrome Treated?

There is no cure for CHARGE Syndrome, since it is reportedly a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can CHARGE Syndrome be Prevented?

Currently, CHARGE Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of CHARGE Syndrome? (Outcomes/Resolutions)

• The prognosis of CHARGE Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

(Source: CHARGE Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for CHARGE Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/