CHD2-Related Syndrome
CHD2-related syndrome is also called developmental and epileptic encephalopathy 94. For this guide, we will be using the name CHD2-related syndrome to encompass the wide range of variants observed in the people identified.
What is CHD2-related syndrome?
CHD2-related syndrome happens when there are changes to the CHD2 gene. These changes can keep the gene from working as it should.
Key Role
The CHD2 gene plays a key role in the brain and body.
Symptoms
Many people who have CHD2-related syndrome have:
- Developmental delay, intellectual disability
- Autism spectrum disorder or symptoms of autism
- Epilepsy that starts at a young age
- Behavioral challenges
What causes CHD2-related syndrome?
CHD2-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the CHD2 gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.
Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.
De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because CHD2 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that CHD2-related syndrome is often the result of a de novo variant in CHD2. Many parents who have had their genes tested do not have the CHD2 genetic variant found in their child who has the syndrome. In some cases, CHD2-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
CHD2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CHD2 they will likely have symptoms of CHD2-related syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.
Autosomal Dominant Genetic Syndrome
Why does my child have a change in the CHD2-related syndrome gene?
No parent causes their child’s CHD2-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.
What are the chances that other family members of future children will have CHD2-related syndrome?
Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.
The risk of having another child who has CHD2-related syndrome depends on the genes of both biological parents.
- If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant.
- If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent.
For a symptom-free brother or sister of someone who has CHD2-related syndrome, the sibling’s risk of having a child who has CHD2-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing CHD2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CHD2-related syndrome.
- If one biological parent has the same genetic variant causing CHD2-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent.
For a person who has CHD2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have CHD2-related syndrome?
As of 2024, at least 307 people with CHD2-related syndrome have been identified in a medical clinic. The first case of CHD2-related syndrome was described in 2012.
Do people who have CHD2-related syndrome look different?
People with CHD2-related syndrome may look different. Appearance can vary and can include, but is not limited to, smaller than average head size and height.
How is CHD2-related syndrome treated?
Scientists and doctors have only just begun to study CHD2-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:
- Physical exams and brain studies. An EEG, or electroencephalogram, which measures the brain’s electrical activity, or an MRI scan, a procedure that shows the structure of the brain, can help diagnose epilepsy and guide treatment.
- Genetics consults
- Development and behavior studies
- Other issues, as needed
A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:
- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for CHD2-related syndrome should begin as early as possible, ideally before a child begins school.
If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/learn/types-seizures.
This section includes a summary of information from major published articles. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and references section of this guide.
Behavior and development concerns linked to CHD2-related syndrome
Learning
Almost everyone with CHD2-related syndrome has intellectual disability, ranging from mild to severe. People who have the syndrome generally need special educational support.
- 91 out of 102 people have mild to severe intellectual disability (89 percent).
Behavior
About one-half of people who have the syndrome have autism. Many people have behavior issues, most often aggression.
- 41 out of 94 are diagnosed with autism (44 percent).
- 17 out of 68 have behavior issues (25 percent).
Medical and physical concerns linked to CHD2-related syndrome
Brain
People who have CHD2-related syndrome might have seizures. Sometimes seizures are caused by fevers or flashing lights. Seizures might not be controlled by medicines. Age of seizure onset can range from 6 months to over 12 years old. Average age of seizure onset is 2 and a half years. In the medical research, there has not been one anti-seizure medication shown to be beneficial to people with CHD2-related syndrome.
More than one-half have seizures that are caused by flashing lights.
- 108 out of 113 have seizures (96 percent).
- 50 out of 88 have seizures caused by flashing lights (57 percent).
Development
More than one-half have developmental delays before seizure onset. More than one-third are shorter than average, and some have scoliosis.
- 61 out of 83 have developmental delays before seizure onset (73 percent).
- 12 out of 34 are shorter than average (35 percent).
- 5 out of 68 have scoliosis (7 percent).
Movement
Some have walking issues or ataxia.
- 7 out of 68 have walking issues (10 percent).
- 7 out of 68 ataxia (10 percent).
Where can I find support and resources?
Coalition to Cure CHD2 (CCC)
Coalition to Cure CHD2 (CCC) is a 100% volunteer-run organization fueled by their desire to help children & others with CHD2-related disorders. Their mission is to improve the lives of those affected by CHD2-related disorders by funding research necessary for uncovering a cure. Their vision is to find safe and effective treatments that will cure CHD2-related disorders.
Simons Searchlight
Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight CHD2 webpage: www.simonssearchlight.org/research/what-we-study/chd2
- Simons Searchlight Facebook group for CHD2 families: www.facebook.com/groups/searchlight.chd2
Other community resources:
- CHD2 Research and Support Group: www.facebook.com/groups/1462485137354985
Sources and References
The content in this guide comes from published studies about CHD2-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Carvill GL, Mefford HC. CHD2-Related Neurodevelopmental Disorders. 2015 Dec 10 [Updated 2021 Jan 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK333201/
- Capelli LP. et al. European Journal of Medical Genetics, 55, 132-134, (2012). Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency www.cbi.nlm.nih.gov/pubmed/22178256
- Epi4K Consortium. et al. Nature, 501, 217-221, (2013). De novo mutations in epileptic encephalopathies www.cbi.nlm.nih.gov/pubmed/23934111
- Feng W, Fang F, Wang X, Chen C, Lu J, Deng J. Clinical analysis of CHD2 gene mutations in pediatric patients with epilepsy. Pediatr Investig. 2022;6(2):93-99. Published 2022 Apr 26. doi:10.1002/ped4.12321
- Suls A. et al. American Journal of Human Genetics, 93, 967-975, (2013). De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome www.ncbi.nlm.nih.gov/pubmed/24207121
- Lund C. et al. Epilepsy & Behavior, 33, 18-21, (2014). CHD2 mutations in Lennox-Gastaut syndrome www.ncbi.nlm.nih.gov/pubmed/24614520
- Thomas RH. et al. Neurology, 84, 951-958, (2015). CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures www.ncbi.nlm.nih.gov/pubmed/25672921
- Wang X, Cui D, Ding C, et al. Novel Loss-of-Function Variants in CHD2 Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients. Genes (Basel). 2022;13(5):908. Published 2022 May 19. doi:10.3390/genes13050908
- Zhu L, Peng F, Deng Z, Feng Z, Ma X. A Novel Variant of the CHD2 Gene Associated With Developmental Delay and Myoclonic Epilepsy. Front Genet. 2022;13:761178. Published 2022 Feb 11. doi:10.3389/fgene.2022.761178