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CHARGE syndrome

Updated : December 27, 2023





Background

CHARGE syndrome is a rare genetic disorder that affects multiple organ systems. The acronym “CHARGE” stands for the most common features of the condition:

C – Coloboma (eye abnormalities)

H – Heart defects

A – Atresia (choanal atresia, a blockage in the nasal passage)

R – Retardation of growth and development

G – Genital and urinary abnormalities

E – Ear abnormalities and hearing loss

In addition to these features, individuals with CHARGE syndrome may also have other health issues, such as feeding and breathing difficulties, neurological problems, and immune system abnormalities. The severity and combination of symptoms can vary widely between individuals, even among those with the same genetic mutation.

CHARGE syndrome is caused by mutations in the CHD7 gene, which provides instructions for making a protein involved in the development and function of many organs and tissues in the body. Most cases of CHARGE syndrome occur sporadically, meaning there is no family history of the condition, but in some cases, it can be inherited in an autosomal dominant pattern.

There is currently no cure for CHARGE syndrome, but treatment and supportive care can help manage symptoms and improve the quality of life for affected individuals. Treatment may include surgical interventions for specific health issues, such as heart defects or choanal atresia, and therapies to address developmental delays or hearing loss.

Epidemiology

CHARGE syndrome is a rare disorder, with an estimated incidence of 1 in 8,500 to 1 in 10,000 live births. It affects both males and females and occurs across all ethnic and racial groups. The prevalence of CHARGE syndrome may be underestimated, as many affected individuals may be undiagnosed or misdiagnosed due to the wide range of symptoms and their variability.

Additionally, some individuals with milder forms of the condition may not meet the diagnostic criteria for CHARGE syndrome. It is also worth noting that CHARGE syndrome has a wide range of clinical manifestations and can affect many different organ systems, making diagnosis and management challenging. However, advances in genetic testing have improved the accuracy and accessibility of diagnosis for CHARGE syndrome.

Anatomy

Pathophysiology

CHARGE syndrome is caused by mutations in the CHD7 gene, which encodes a protein that is involved in the regulation of gene expression during embryonic development. The CHD7 protein plays a critical role in the formation and maintenance of many different tissues and organs, including the inner ear, eyes, heart, and cranial nerves. The exact mechanism by which CHD7 mutations lead to the features of CHARGE syndrome is not fully understood, but it is thought to involve disruptions in the development of these tissues and organs.

The eye abnormalities (coloboma) seen in CHARGE syndrome are thought to result from abnormal development of the optic nerve and retina, which are both derived from the same embryonic tissue. The heart defects may be due to abnormal development of the cardiac neural crest cells, which give rise to the heart and other tissues. The choanal atresia (blockage of the nasal passage) may result from abnormal development of the nasal cavity and cranial nerves.

Ear abnormalities and hearing loss are thought to result from defects in the development of the inner ear. In addition to these specific features, CHARGE syndrome may also affect the development of other tissues and organs throughout the body. The overall pathophysiology of CHARGE syndrome is complex and involves a combination of developmental abnormalities in multiple organ systems.

Etiology

CHARGE syndrome is a genetic disorder that is caused by mutations in the CHD7 gene. This gene provides instructions for making a protein that is involved in the regulation of gene expression during embryonic development. Most cases of CHARGE syndrome are caused by de novo mutations, meaning that the mutation occurs spontaneously and is not inherited from either parent.

However, in rare cases, CHARGE syndrome can be inherited in an autosomal dominant pattern, which means that one copy of the mutated gene is sufficient to cause the disorder. In these cases, a parent with CHARGE syndrome has a 50% chance of passing the mutated gene on to each of their children.

Genetics

Prognostic Factors

The prognosis for individuals with CHARGE syndrome varies widely depending on the severity and combination of symptoms present. Some individuals may have mild symptoms and a good prognosis, while others may have severe disabilities and a reduced life expectancy.

Complications associated with CHARGE syndrome, such as heart defects and breathing difficulties, can increase the risk of mortality. However, with appropriate management of symptoms and timely medical interventions, many individuals with CHARGE syndrome are able to lead fulfilling lives and achieve developmental milestones.

As research on CHARGE syndrome continues, advances in understanding the underlying genetics and pathophysiology of the condition may lead to improved prognoses and treatment options for affected individuals.

Clinical History

Clinical presentation

CHARGE syndrome is a complex genetic disorder that can affect multiple systems in the body. The clinical presentation can vary widely, but there are several common features that are often present. These features may not be present in every individual with CHARGE syndrome, and the severity can also vary.

Coloboma: A coloboma is a defect in the eye that occurs when the eye does not fully develop. This can cause vision problems or blindness.

Heart defects: Many individuals with CHARGE syndrome have congenital heart defects, which can include atrial septal defect, ventricular septal defect, or tetralogy of Fallot.

Atresia of the choanae: Atresia of the choanae is a condition in which the back of the nasal passages is blocked, which can cause breathing difficulties.

Retardation of growth and development: Children with CHARGE syndrome may have delayed growth and development, including delayed motor skills, speech and language delays, and intellectual disability.

Genital and urinary anomalies: Many individuals with CHARGE syndrome have abnormalities of the genital and urinary systems, including undescended testes, hypospadias, and kidney abnormalities.

Ear anomalies: Ear abnormalities are common in CHARGE syndrome and can include hearing loss, malformations of the ear canal, and absence of the inner ear.

Cranial nerve anomalies: CHARGE syndrome can affect several cranial nerves, including the facial nerve, which can cause facial weakness or paralysis.

Tracheoesophageal anomalies: Some individuals with CHARGE syndrome have tracheoesophageal anomalies, which can cause feeding difficulties and respiratory problems.

The features of CHARGE syndrome can vary widely between individuals, and some individuals may have additional features not listed here. A diagnosis of CHARGE syndrome is usually based on the presence of several characteristic features and may require genetic testing to confirm the diagnosis.

Physical Examination

Physical examination

CHARGE syndrome is a complex genetic disorder that affects multiple organ systems, so physical examination can reveal a wide range of abnormalities. Some of the physical features that may be present in individuals with CHARGE syndrome include:

Craniofacial anomalies: Individuals with CHARGE syndrome may have craniofacial abnormalities such as a small or underdeveloped jaw, narrow or underdeveloped ear canals, and cleft lip or palate.

Eye abnormalities: Eye abnormalities such as coloboma (a gap in the iris or retina), ptosis (drooping of the upper eyelid), and strabismus (crossed eyes) may be present.

Ear anomalies: Ear anomalies may include external ear abnormalities, hearing loss, and absence or malformation of the inner ear structures.

Cardiovascular abnormalities: Individuals with CHARGE syndrome may have cardiovascular abnormalities such as atrial or ventricular septal defects (holes in the walls separating the heart chambers), patent ductus arteriosus (a blood vessel that fails to close after birth), or tetralogy of Fallot (a complex heart defect).

Gastrointestinal anomalies: Gastrointestinal anomalies such as esophageal atresia (a condition where the esophagus does not connect to the stomach), tracheoesophageal fistula (an abnormal connection between the esophagus and trachea), and intestinal malrotation (a condition where the intestines do not develop in the correct position) may be present.

Genitourinary anomalies: Genitourinary anomalies may include kidney abnormalities, hypospadias (a condition where the urethra does not open at the tip of the penis), and cryptorchidism (undescended testicles).

Growth and developmental delays: Children with CHARGE syndrome may have growth and developmental delays, including delayed motor development, intellectual disability, and behavioral problems.

It is important to note that not all individuals with CHARGE syndrome will have all of these physical features, and the severity of these features can vary widely between individuals.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential diagnosis

The clinical features of CHARGE syndrome can overlap with other genetic syndromes and disorders, making differential diagnosis important. Some of the conditions that can be considered in the differential diagnosis of CHARGE syndrome include:

VACTERL association: A syndrome that involves vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities.

Kabuki syndrome: A genetic condition that involves intellectual disability, distinctive facial features, skeletal abnormalities, and a range of other symptoms.

Goldenhar syndrome: A congenital disorder that affects the development of the face, eyes, and ears.

Oculoauriculovertebral syndrome (OAVS): A condition that involves abnormalities of the eyes, ears, and vertebrae.

DiGeorge syndrome: A genetic disorder that affects the development of several organs and systems in the body, including the heart, thymus gland, and parathyroid glands.

Treacher Collins syndrome: A rare genetic disorder that affects the development of the bones and tissues of the face.

Noonan syndrome: A genetic condition that affects multiple systems in the body, including the heart, eyes, and skeletal system.

Mowat-Wilson syndrome: A genetic disorder that involves intellectual disability, distinctive facial features, and other symptoms.

It is important to consider these conditions in the differential diagnosis of CHARGE syndrome to ensure accurate diagnosis and appropriate management.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Currently, there is no cure for CHARGE syndrome and treatment is mainly supportive and aimed at managing the various symptoms and complications that may arise. Treatment options may vary depending on the individual’s specific needs and may involve a multidisciplinary team of healthcare professionals.

Some common treatment options for CHARGE syndrome include:

Surgical intervention: Individuals with CHARGE syndrome may require surgery to address some of the physical abnormalities associated with the disorder, such as cleft lip or palate, heart defects, or tracheoesophageal abnormalities.

Hearing aids and cochlear implants: Individuals with CHARGE syndrome may experience hearing loss and may benefit from the use of hearing aids or cochlear implants.

Speech therapy: Many individuals with CHARGE syndrome experience speech and language delays and may require speech therapy to help them communicate effectively.

Vision therapy: Individuals with CHARGE syndrome may experience vision problems, such as strabismus or nystagmus, and may benefit from vision therapy or corrective lenses.

Feeding therapy: Infants with CHARGE syndrome may experience difficulties with feeding and may require specialized feeding therapy to help them eat and drink properly.

Management of developmental delays: Individuals with CHARGE syndrome may experience developmental delays and may require early intervention services to help them reach their developmental milestones.

Management of behavioral and emotional issues: Some individuals with CHARGE syndrome may experience behavioral or emotional issues, such as anxiety or ADHD, and may require therapy or medication to manage these issues.

It is important for individuals with CHARGE syndrome to have regular medical check-ups and to receive ongoing care from a team of healthcare professionals to ensure their overall health and well-being.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK559199/

CHARGE syndrome

Updated : December 27, 2023




CHARGE syndrome is a rare genetic disorder that affects multiple organ systems. The acronym “CHARGE” stands for the most common features of the condition:

C – Coloboma (eye abnormalities)

H – Heart defects

A – Atresia (choanal atresia, a blockage in the nasal passage)

R – Retardation of growth and development

G – Genital and urinary abnormalities

E – Ear abnormalities and hearing loss

In addition to these features, individuals with CHARGE syndrome may also have other health issues, such as feeding and breathing difficulties, neurological problems, and immune system abnormalities. The severity and combination of symptoms can vary widely between individuals, even among those with the same genetic mutation.

CHARGE syndrome is caused by mutations in the CHD7 gene, which provides instructions for making a protein involved in the development and function of many organs and tissues in the body. Most cases of CHARGE syndrome occur sporadically, meaning there is no family history of the condition, but in some cases, it can be inherited in an autosomal dominant pattern.

There is currently no cure for CHARGE syndrome, but treatment and supportive care can help manage symptoms and improve the quality of life for affected individuals. Treatment may include surgical interventions for specific health issues, such as heart defects or choanal atresia, and therapies to address developmental delays or hearing loss.

CHARGE syndrome is a rare disorder, with an estimated incidence of 1 in 8,500 to 1 in 10,000 live births. It affects both males and females and occurs across all ethnic and racial groups. The prevalence of CHARGE syndrome may be underestimated, as many affected individuals may be undiagnosed or misdiagnosed due to the wide range of symptoms and their variability.

Additionally, some individuals with milder forms of the condition may not meet the diagnostic criteria for CHARGE syndrome. It is also worth noting that CHARGE syndrome has a wide range of clinical manifestations and can affect many different organ systems, making diagnosis and management challenging. However, advances in genetic testing have improved the accuracy and accessibility of diagnosis for CHARGE syndrome.

CHARGE syndrome is caused by mutations in the CHD7 gene, which encodes a protein that is involved in the regulation of gene expression during embryonic development. The CHD7 protein plays a critical role in the formation and maintenance of many different tissues and organs, including the inner ear, eyes, heart, and cranial nerves. The exact mechanism by which CHD7 mutations lead to the features of CHARGE syndrome is not fully understood, but it is thought to involve disruptions in the development of these tissues and organs.

The eye abnormalities (coloboma) seen in CHARGE syndrome are thought to result from abnormal development of the optic nerve and retina, which are both derived from the same embryonic tissue. The heart defects may be due to abnormal development of the cardiac neural crest cells, which give rise to the heart and other tissues. The choanal atresia (blockage of the nasal passage) may result from abnormal development of the nasal cavity and cranial nerves.

Ear abnormalities and hearing loss are thought to result from defects in the development of the inner ear. In addition to these specific features, CHARGE syndrome may also affect the development of other tissues and organs throughout the body. The overall pathophysiology of CHARGE syndrome is complex and involves a combination of developmental abnormalities in multiple organ systems.

CHARGE syndrome is a genetic disorder that is caused by mutations in the CHD7 gene. This gene provides instructions for making a protein that is involved in the regulation of gene expression during embryonic development. Most cases of CHARGE syndrome are caused by de novo mutations, meaning that the mutation occurs spontaneously and is not inherited from either parent.

However, in rare cases, CHARGE syndrome can be inherited in an autosomal dominant pattern, which means that one copy of the mutated gene is sufficient to cause the disorder. In these cases, a parent with CHARGE syndrome has a 50% chance of passing the mutated gene on to each of their children.

The prognosis for individuals with CHARGE syndrome varies widely depending on the severity and combination of symptoms present. Some individuals may have mild symptoms and a good prognosis, while others may have severe disabilities and a reduced life expectancy.

Complications associated with CHARGE syndrome, such as heart defects and breathing difficulties, can increase the risk of mortality. However, with appropriate management of symptoms and timely medical interventions, many individuals with CHARGE syndrome are able to lead fulfilling lives and achieve developmental milestones.

As research on CHARGE syndrome continues, advances in understanding the underlying genetics and pathophysiology of the condition may lead to improved prognoses and treatment options for affected individuals.

Clinical presentation

CHARGE syndrome is a complex genetic disorder that can affect multiple systems in the body. The clinical presentation can vary widely, but there are several common features that are often present. These features may not be present in every individual with CHARGE syndrome, and the severity can also vary.

Coloboma: A coloboma is a defect in the eye that occurs when the eye does not fully develop. This can cause vision problems or blindness.

Heart defects: Many individuals with CHARGE syndrome have congenital heart defects, which can include atrial septal defect, ventricular septal defect, or tetralogy of Fallot.

Atresia of the choanae: Atresia of the choanae is a condition in which the back of the nasal passages is blocked, which can cause breathing difficulties.

Retardation of growth and development: Children with CHARGE syndrome may have delayed growth and development, including delayed motor skills, speech and language delays, and intellectual disability.

Genital and urinary anomalies: Many individuals with CHARGE syndrome have abnormalities of the genital and urinary systems, including undescended testes, hypospadias, and kidney abnormalities.

Ear anomalies: Ear abnormalities are common in CHARGE syndrome and can include hearing loss, malformations of the ear canal, and absence of the inner ear.

Cranial nerve anomalies: CHARGE syndrome can affect several cranial nerves, including the facial nerve, which can cause facial weakness or paralysis.

Tracheoesophageal anomalies: Some individuals with CHARGE syndrome have tracheoesophageal anomalies, which can cause feeding difficulties and respiratory problems.

The features of CHARGE syndrome can vary widely between individuals, and some individuals may have additional features not listed here. A diagnosis of CHARGE syndrome is usually based on the presence of several characteristic features and may require genetic testing to confirm the diagnosis.

Physical examination

CHARGE syndrome is a complex genetic disorder that affects multiple organ systems, so physical examination can reveal a wide range of abnormalities. Some of the physical features that may be present in individuals with CHARGE syndrome include:

Craniofacial anomalies: Individuals with CHARGE syndrome may have craniofacial abnormalities such as a small or underdeveloped jaw, narrow or underdeveloped ear canals, and cleft lip or palate.

Eye abnormalities: Eye abnormalities such as coloboma (a gap in the iris or retina), ptosis (drooping of the upper eyelid), and strabismus (crossed eyes) may be present.

Ear anomalies: Ear anomalies may include external ear abnormalities, hearing loss, and absence or malformation of the inner ear structures.

Cardiovascular abnormalities: Individuals with CHARGE syndrome may have cardiovascular abnormalities such as atrial or ventricular septal defects (holes in the walls separating the heart chambers), patent ductus arteriosus (a blood vessel that fails to close after birth), or tetralogy of Fallot (a complex heart defect).

Gastrointestinal anomalies: Gastrointestinal anomalies such as esophageal atresia (a condition where the esophagus does not connect to the stomach), tracheoesophageal fistula (an abnormal connection between the esophagus and trachea), and intestinal malrotation (a condition where the intestines do not develop in the correct position) may be present.

Genitourinary anomalies: Genitourinary anomalies may include kidney abnormalities, hypospadias (a condition where the urethra does not open at the tip of the penis), and cryptorchidism (undescended testicles).

Growth and developmental delays: Children with CHARGE syndrome may have growth and developmental delays, including delayed motor development, intellectual disability, and behavioral problems.

It is important to note that not all individuals with CHARGE syndrome will have all of these physical features, and the severity of these features can vary widely between individuals.

Differential diagnosis

The clinical features of CHARGE syndrome can overlap with other genetic syndromes and disorders, making differential diagnosis important. Some of the conditions that can be considered in the differential diagnosis of CHARGE syndrome include:

VACTERL association: A syndrome that involves vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities.

Kabuki syndrome: A genetic condition that involves intellectual disability, distinctive facial features, skeletal abnormalities, and a range of other symptoms.

Goldenhar syndrome: A congenital disorder that affects the development of the face, eyes, and ears.

Oculoauriculovertebral syndrome (OAVS): A condition that involves abnormalities of the eyes, ears, and vertebrae.

DiGeorge syndrome: A genetic disorder that affects the development of several organs and systems in the body, including the heart, thymus gland, and parathyroid glands.

Treacher Collins syndrome: A rare genetic disorder that affects the development of the bones and tissues of the face.

Noonan syndrome: A genetic condition that affects multiple systems in the body, including the heart, eyes, and skeletal system.

Mowat-Wilson syndrome: A genetic disorder that involves intellectual disability, distinctive facial features, and other symptoms.

It is important to consider these conditions in the differential diagnosis of CHARGE syndrome to ensure accurate diagnosis and appropriate management.

Currently, there is no cure for CHARGE syndrome and treatment is mainly supportive and aimed at managing the various symptoms and complications that may arise. Treatment options may vary depending on the individual’s specific needs and may involve a multidisciplinary team of healthcare professionals.

Some common treatment options for CHARGE syndrome include:

Surgical intervention: Individuals with CHARGE syndrome may require surgery to address some of the physical abnormalities associated with the disorder, such as cleft lip or palate, heart defects, or tracheoesophageal abnormalities.

Hearing aids and cochlear implants: Individuals with CHARGE syndrome may experience hearing loss and may benefit from the use of hearing aids or cochlear implants.

Speech therapy: Many individuals with CHARGE syndrome experience speech and language delays and may require speech therapy to help them communicate effectively.

Vision therapy: Individuals with CHARGE syndrome may experience vision problems, such as strabismus or nystagmus, and may benefit from vision therapy or corrective lenses.

Feeding therapy: Infants with CHARGE syndrome may experience difficulties with feeding and may require specialized feeding therapy to help them eat and drink properly.

Management of developmental delays: Individuals with CHARGE syndrome may experience developmental delays and may require early intervention services to help them reach their developmental milestones.

Management of behavioral and emotional issues: Some individuals with CHARGE syndrome may experience behavioral or emotional issues, such as anxiety or ADHD, and may require therapy or medication to manage these issues.

It is important for individuals with CHARGE syndrome to have regular medical check-ups and to receive ongoing care from a team of healthcare professionals to ensure their overall health and well-being.

https://www.ncbi.nlm.nih.gov/books/NBK559199/