CHARGE syndrome

Changes in the CHD7 gene are responsible for CHARGE syndrome. Normally, this gene is very active during the early development of the embryo, particularly in the brain, eye, and inner ear. The gene also provides the instructions for proper creation and functioning of nerves involved in the ability to smell. Changes (mutations) in the gene cause can cause it to stop working. This causes the embryo to develop improperly, causing the symptoms seen in the disorder.

There are several different tests that may be utilized to determine if an individual has CHARGE syndrome. This includes:

After being diagnosed with CHARGE syndrome, children should be evaluated for common features of the condition. This evaluation includes a combination of tests and exams usually performed or ordered by a medical geneticist. Next, an overall monitoring and treatment plan can then be designed to fit the child’s needs. Treatment typically includes being cared for by a number of specialists such as a cardiologist (heart doctor), endocrinologist (hormone doctor), craniofacial surgeon, physical therapies, and geneticist. Depending on which specialists are involved, doctors may make additional recommendations to evaluate children for the associated features of CHARGE syndrome.

Treatments for CHARGE syndrome depend on the medical issues affecting the individual.. Thus, the first step towards treatment involves assessments by various specialists followed by management of those symptoms. Cleft lip, choanal atresia, and/or heart defects are often surgically corrected. Children with a tracheoesophageal fistula may require surgery and additional management. Feeding problems and speech/language delays are addressed via therapies such as speech, physical, and occupational therapy. Sleep disturbances and obstructive sleep apnea issues are evaluated by a sleep study and treated by standard treatments. Other specialists who often are involved in the care and treatment of children with CHARGE syndrome include genetics, cardiology, audiology and ENT, ophthalmology, urology, and endocrinology.

CHARGE syndrome is a condition that is characterized by medical issues in several parts of the body and changes in the development of the brain. The letters forming the condition’s name "CHARGE" are an acronym as each letter stands for a specific feature of the condition:

CHARGE syndrome is most often caused by genetic changes in the CHD7 gene. This makes sense as the CHD7 gene is important in organizing the early development of many parts of the body including the brain, eye, and inner ear. The gene also provides the instructions for proper creation and functioning of nerves involved in the ability to smell. Interestingly, some individuals with certain changes in the CHD7 gene may have a different medical condition such as Kallman syndrome rather than a diagnosis of CHARGE syndrome.

However, genetic testing for CHARGE syndrome will only detect changes in the CHD7 gene in approximately 60-70% of people with the symptoms of the disorder. This means that individuals can have CHARGE syndrome without a change in CHD7 gene. Further research is ongoing as there may be another gene that also leads to the condition or another genetic condition that looks like CHARGE syndrome.

A variant of unknown significance is a genetic change that has not been seen before. More specifically, the change hasn’t been seen in people known to have the condition, and it also hasn’t been seen in healthy people. There is not enough information to know if that particular change within the gene is enough to cause the disorder, or if it is a normal variation that does not cause any problems.

We all have variations in our genes and variants of unknown significance are changes that we cannot tell if they are medically significant or not. Additional testing may be recommended by your doctor to further clarify if a particular variant of unknown significance is medically significant or not. Otherwise, it is important to work with your doctor to check in with the laboratory from time to time to ask if the gene has been reclassified as disease-causing or not.

Management of a child or individual with CHARGE Syndrome may require several different specialists including:

Clinical trials for CHARGE syndrome can be found via the ClinicalTrials.Gov website. The CHARGE syndrome foundation also has information about enrolling or ongoing clinical trials on their webpage.

CHARGE syndrome is named for the main features of the condition. This includes coloboma, heart defects, choanal atreasia, retarded growth and development, genital abnormalities, and ear anomalies.

If a child or family member tests positive for CHARGE syndrome, testing may be completed on the parents of the child.
Next, if parental testing is positive, a genetic counselor and/or geneticist can help identify who else in the family is at risk of having CHARGE syndrome.

If parental testing is negative, this typically means that the child or individual with CHARGE syndrome is the first person in their family with the condition. Therefore, other family members may not have an increased risk to have a child or be affected with CHARGE syndrome. In this case, testing other people may not be necessary. Discussing these concerns with a genetic counselor and geneticist is recommended. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Because CHARGE syndrome is inherited in an autosomal dominant inheritance pattern, it means that every first degree relative of an affected individual has a 50% chance of also inheriting the condition. First degree relatives are siblings, children, and parents. Second degree relatives should have testing after first degree relatives are all tested.

In a specific example, let’s say 27-year-old Andrea has been diagnosed with CHARGE syndrome. Andrea has 3 children. EACH of her children has an individual 50% chance to also have it. Andrea has 2 siblings: one brother and one sister. EACH of her siblings has an individual 50% chance to also have it. Andrea’s mother has testing and is negative. This means that Andrea’s mother’s side of the family does NOT need to have any more testing. Andrea’s father has testing and is positive. Each of Andrea’s father’s siblings should have testing as well, because they have an individual 50% chance of being positive as well.

CHARGE syndrome is due to a change in the DNA. There is nothing that the mother or father may have done prior to pregnancy or during a pregnancy to cause CHARGE syndrome.

If a CHD7 mutation is identified in a person with CHARGE syndrome, it is possible to test other people (or pregnancies or pre-implantation embryos) for that same gene. Genetic counselors are specially trained to help individuals understand genetic testing options before and during pregnancy. It is very helpful to meet with them prior to being tested for CHARGE syndrome. In the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

The CHARGE Syndrome Foundation (http://www.chargesyndrome.org/) is a support group designated to helping others understand more about CHARGE Syndrome and identify resources, medical care, and support.

Each doctor or specialist that sees a child with CHARGE Syndrome may have a different role in the management of that individual’s medical concerns. Therefore, each specialist may have different aspects of the condition that they are more aware of than other specialists. A geneticist and/or genetic counselor can assist you with identifying specialists who may be more familiar with the treatment and management of a child with CHARGE syndrome. Additionally, many individuals require specialized care for their child with CHARGE syndrome and therefore, their primary care doctors or pediatricians may refer you to the appropriate specialist instead. A geneticist and/or genetic counselor can assist you in identifying resources, medical literature articles and coordinating your child’s care with their other specialists. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

The CHARGE syndrome foundation has additional resources on their website that describe the role of each specialist on the team.

CHARGE syndrome has variable expressivity, meaning that some people who have CHARGE syndrome may have different symptoms than others. The frequency of each symptom has been found to occur:

CHARGE syndrome is caused by changed in the CHD7 gene. This can be a single letter change within the DNA of the gene or because of a large deletion (or missing copy) of the CHD7 gene.

CHARGE syndrome may be inherited, or may be a brand new change in one person.

Most individuals with CHARGE syndrome have not inherited their change in the CHD7 gene from a parent. Instead, it was a spontaneous and new (de novo) change that occurred for the first time in them and there is no one else in the family with CHARGE syndrome. New changes in the CHD7 gene can occur randomly (by chance) in the egg or sperm, at conception, or during early stages of an embryo.

Sometimes, a person will inherit a change in the CHD7 gene from a parent who also has CHARGE syndrome.

CHARGE syndrome is an autosomal dominant condition, because only one of the two copies of the CHD7 gene needs to have a change to cause the disorder. This means that individuals with CHARGE syndrome have a 50% (or a 1 in 2) risk to pass on that change to each of their pregnancies.

Diagnostic criteria for CHARGE syndrome is based on a combination of physical findings and health issues called "major and minor diagnostic characteristics". CHARGE syndrome is confirmed as a diagnosis in individuals with all four major characteristics OR three major and three minor characteristics. Probable/possible CHARGE syndrome is considered in individuals with one or two major characteristics and several minor characteristics.

Major characteristics are:

The diagnosis of CHARGE syndrome begins from a combination of a physical exam and other tests. After the clinical diagnosis of CHARGE syndrome is suspected or confirmed genetic testing can help clarify things. Most specialists encourage you to meet with a genetic counselor and/or geneticist before testing to ensure that the correct test is being ordered.

Testing usually involves taking a small sample of blood or saliva and sending it to a lab that specializes in testing for genetic conditions. There are several different tests that may be utilized to determine if an individual has CHARGE syndrome. These include:

Clinical research opportunities for CHARGE syndrome can be located through the clinicaltrials.gov website or through the CHARGE Syndrome Foundation Website (http://www.chargesyndrome.org/research/opportunities-for-families/).

In Europe, the EU Clinical Trial Register performs a similar service.

The CHARGE syndrome Foundation website has great resources for parents of those who have CHARGE syndrome. Their website has a section about transition into adulthood, which can be found here. They list a lot of great resources that will help you navigate this time.

Donations to research opportunities can be explored through the CHARGE Syndrome Foundation’s donation webpage.

You can locate or connect with others with CHARGE syndrome and their family members, friends and caretakers through a national support group, like the CHARGE Syndrome Foundation. Additionally, some individuals connect through social media websites such as Facebook.com, Instagram, and/or Caring Bridge.

It is estimated that CHARGE syndrome is seen in one in 10,000 births to one in 8,500 live births.

Children with CHARGE syndrome who have hearing and vision issues often can benefit from having a communication device. The National Center on deaf and blindness may be a helpful resource in locating available options for a communication device for your child. Additionally, a number of medical specialists have access to case and social workers that can assist you with identifying resources to obtain a communication device for your child. Some families also work directly with their school district, early intervention or education planner, and/or therapists to obtain a communication device for their child.

Hospitals or institutions that have doctors who specialize in treating individuals with CHARGE syndrome can be located through the CHARGE Syndrome Foundation’s website.

You can also locate a genetics clinic experienced with CHARGE Syndrome through the American College of Medical Genetics. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website .

Genetic testing for CHARGE syndrome typically is completed on a blood sample; however, saliva may be an option as well. A genetic expert can help determine the lab requirements for testing. Genetic counselors are specially trained to help individuals understand genetic testing and results. It is very helpful to meet with them prior to being tested for CHARGE syndrome. In the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

CHARGE syndrome does not appear occur more frequently in certain populations or in a specific ethnicity.

The changes in development seen in CHARGE syndrome happen before birth and at this time there is nothing that can be done during the pregnancy that could have changed or prevented the features of syndrome. After birth, symptom specific treatments can help people living with CHARGE syndrome. For example, cleft lip or heart defects can be surgically corrected. Others, such as feeding problems and speech and language deficits can be addressed with physical, occupational, and speech therapy.

Some children or individuals with CHARGE syndrome are diagnosed with autism or they may have behavioral concerns that overlap with CHARGE syndrome such as a sensory processing disorder, certain sound or texture aversions, ADHD, intellectual disabilities and/or anxiety or obsessive compulsive disorder.

Not every child or individual with CHARGE syndrome will have or develop these concerns, however, they are a reported medical feature or association with the diagnosis of CHARGE syndrome. The CHARGE syndrome foundation has excellent resources on behavior and autism on their website.

Children or individuals with CHARGE syndrome may qualify for an IEP program through their school district. They may also qualify for a 504 plan, which is a separate educational planning tool that allows for special accommodations due to a child’s medical concerns. This may include things like allowing a child to eat their meals with the school nurse to ensure adequate nutrition, use an elevator instead of the stairs if their are mobility constraints, etc. The CHARGE syndrome foundation has excellent resources on CHARGE related educational topics.

CHARGE syndrome affects each child in a unique way. Some children do very well in standard schools. However, many children with CHARGE syndrome have many unique needs. Some school districts are able to make the necessary accommodations to help children with CHARGE syndrome, while others do not have the necessary resources. It is important to reach out to your child’s school district early in the process of enrollment to determine the best options for them. It is also important to have evaluations that can predict any specific support needed and are tailor to a specific child. In children with vision and/or hearing issues, standard assessments may need to be modified to fully understand their needs. Some children with CHARGE syndrome may benefit from attending a school for the deaf and/or blind.

Many children with CHARGE syndrome will likely qualify for an IEP (individualized education plan) and/or a 504 plan (a specialized plan with the school district to accommodate any medical concerns they may have). Public school districts that receive federal funding are required by law to work with you to understand your child’s medical concerns and identify and provide appropriate resources for them. Private schools that do not receive such funding may be limited in the resources they can provide and are not required by law to do so.

It is possible that to have CHARGE syndrome without having a CHD7 gene mutation. Genetic testing does not pick up 100% of mutations, so it is possible that genetic testing will come back negative even though somebody has CHARGE syndrome. A clinical evaluation is the best way to establish a diagnosis that will lead to getting care for CHARGE syndrome.

It is possible to have a mutation in the CHD7 gene and not have CHARGE syndrome. There are some genetic changes in our bodies that are considered benign and do not affect the way that proteins are formed. Benign changes in the CHD7 gene will not lead to a diagnosis of CHARGE syndrome. Additionally, some individuals with certain changes in the CHD7 gene may have a different medical condition such as Kallman syndrome rather than a diagnosis of CHARGE syndrome.

Genetic testing for CHARGE syndrome will detect DNA changes in approximately 60-70% of people with the symptoms of the disorder.

This means that individuals can have CHARGE syndrome and may have negative genetic testing. This could be because:

CHARGE syndrome affects each child in a unique way. Some children do very well in standard schools. However, many children with CHARGE syndrome have many unique needs and success in a local school depends on the resources available to a child through the school district and whether or not they would be able to accommodate a child’s medical, social and academic needs. Parents of children with CHARGE syndrome should consider starting the educational planning process early to explore options for their child’s educational needs. Children with CHARGE syndrome often experience vision and/or hearing deficits that they may benefit more from attending a specialized school for children with these medical concerns that can provide a greater level of resources or assistance. Many private schools do not receive federal funding that requires them by law to accommodate your child’s medical concerns in the academic setting and therefore may not be the best option when exploring educational options.

The CHARGE syndrome foundation has excellent resources on CHARGE related educational topics.

About one-third of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. Researchers believe that other genetic and environmental factors may be involved in these individuals developing CHARGE syndrome that we don’t fully understand. However, as CHARGE syndrome caused in most cases by genetic errors, it is technically always a genetic condition. However, it may not always be inherited from parents. It is possible for syndromes to appear seemingly out of nowhere in a family; we call these mutations de novo mutations. De novo CHARGE syndrome mutations may occur from a genetic change before birth or de novo balanced chromosome rearrangement, specifically called t(8;13)(q11.2;q22). This is when a part of the 13th chromosome and a part of the 8th chromosome switch places and involve the CHD7 gene.

CHARGE syndrome affects each child in a unique way. Accordingly, there are different aspects of the transition from childhood to adulthood that may need be addressed and supported. Some individuals living with CHARGE syndrome will need support and training as they take over the organization of their medical care as an adult. Many pediatric hospitals have resources to help teens with chronic disease take care of their care. Great resource can also be found at the Got Transition? website.

When thinking about future jobs and living, school districts should have educators and social workers that can assist with the process of transitioning children who need help from the school setting to adulthood. Some children living with CHARGE syndrome may qualify for vocational or life skills training that allows them the ability to have a job following graduation from high school.

Other children may require additional assistance and/or may not be capable of independent living or able to work. Therefore, some families may choose to meet with a special needs legal advocate to explore available options for long-term care. The CHARGE syndrome foundation has excellent resources on their focused webpages.

There are different types of changes that can happen in the CHD7 to cause CHARGE syndrome that may include:

CHARGE syndrome in the past was also known as:

There are many genetic conditions that have features or medical concerns that are similar to CHARGE syndrome. These may include:

Depending on a child’s medical concerns, there are specific treatments for specific medical issues. For example a child with hearing loss may be prescribed hearing aids. Other features of CHARGE syndrome may require surgery, while others may focus on therapies to maximize a child’s outcomes, but not necessarily cure or fix that particular medical concern.

The CHARGE syndrome foundation has an excellent management manual for parents that discusses possible complications and the specialists and treatments needed.

About one-third of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. Researchers believe that other genetic and environmental factors may be involved in these individuals developing CHARGE syndrome or there may be other unknown genetic factors to still be discovered.

CHARGE syndrome is a broad diagnosis. People with CHARGE syndrome may be mildly affected, very affected, or somewhere in between. Every individual is affected differently, even though they have the same disorder.

CHARGE syndrome is not a disorder that is included on newborn screening, and therefore newborns are not screened or tested for this condition at birth. If there is a concern or suspicion that an infant may have CHARGE syndrome at birth, the doctor’s taking care of your baby may recommend testing. A genetic counselor and/or geneticist may assist in the process of ordering testing for CHARGE syndrome in the newborn period.

There are many research studies that are looking at comprehensive sequencing testing for infants and children born with birth defects that require a hospital stay in the NICU (neonatal intensive care unit); the CHD7 gene may be included as a part of these types of research studies.

Genetic counselors are specially trained to help individuals understand genetic testing options and results. In the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

CHARGE syndrome affects each child in a unique way; however, most children with CHARGE have limited vision and/or hearing. The sensory losses (hearing, vision, balance), time lost to surgeries, and frequent illness have a huge effect on the child’s exposure to the stimulation that shapes cognitive abilities and other skills. Many children with complex medial issues to be delayed. The goal with such children is to support them via focused educational support and therapies such as speech and occupational and help them reach their highest potential.

The CHARGE syndrome Foundation website has great resources for parents of those who have CHARGE syndrome. Their website has a section about this topic here

CHARGE syndrome affects each child in a unique way; however, most children with CHARGE have limited vision and/or hearing. Legal blindness does not mean the inability to see anything. Even significant hearing loss can often be helped with aids of various sorts. In the early stages of a newborn’s life, it is difficult to predict eventual vision and hearing abilities. The early predictions a parent is given may not turn out to be accurate. Routine visits to pediatric ophthalmology, ENT and audiology will help uncover your child’s abilities.

The CHARGE syndrome Foundation website has great resources for parents of those who have CHARGE syndrome. Their website has a section about this topic here