ARID1B-Related Syndrome
ARID1B-related syndrome is also called Coffin-Siris syndrome 1. For this webpage, we will be using the name ARID1B-related syndrome to encompass the wide range of variants observed in the people identified.
What is ARID1B-related syndrome?
ARID1B-related syndrome happens when there are changes to the ARID1B gene. These changes can keep the gene from working as it should.
ARID1B is a Coffin-Siris gene. Coffin-Siris syndrome can be caused by variants in the following genes: ARID1A, SMARCA2, SMARCA4, SMARCB1, SMARCC2, and SMARCE1.
Key Role
The ARID1B gene helps to control other genes that are important for brain growth.
Symptoms
Because the ARID1B gene is important for brain activity, many people who have ARID1B-related syndrome have:
- Developmental delay
- Intellectual disability
- Speech and language delays
- Behavior issues, including autism and attention-deficit/hyperactivity disorder (ADHD)
- Seizures
- Brain changes seen on magnetic resonance imaging (MRI)
- Low muscle tone
- Feeding difficulties
- Hearing issues
- Impairment of vision
What causes ARID1B-related syndrome?
ARID1B-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 ARID1B 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 ARID1B plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that ARID1B-related syndrome is often the result of a de novo variant in ARID1B. Many parents who have had their genes tested do not have the ARID1B genetic variant found in their child who has the syndrome. In some cases, ARID1B-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
ARID1B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in ARID1B they will likely have symptoms of ARID1B-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 ARID1B gene?
No parent causes their child’s ARID1B-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 ARID1B-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 ARID1B-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 ARID1B-related syndrome, the sibling’s risk of having a child who has ARID1B-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing ARID1B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit ARID1B-related syndrome.
- If one biological parent has the same genetic variant causing ARID1B-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 ARID1B-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have ARID1B-related syndrome?
As of 2026, about 640 people in the world with changes in the ARID1B gene have been identified in a medical clinic. The first case of ARID1B-related syndrome was described in 2012. Scientists expect to find more people who have the syndrome as access to genetic testing improves.
Do people who have ARID1B-related syndrome look different?
People with ARID1B-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:
- Low hairline
- Thick eyebrows
- Long eyelashes
- Wide bridge of the nose
- Large mouth
- Excessive hair growth
How is ARID1B-related syndrome treated?
Scientists and doctors have only just begun to study ARID1B-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
- 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 ARID1B-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: www.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 ARID1B-related syndrome
Learning and speech
Most people with ARID1B-related syndrome had developmental delay or intellectual disability. Many people had speech and language delays. A few people were nonverbal.
- 131 out of 143 people had speech and language delay (92 percent)
The severity of intellectual disability varied among people:
- 39 out of 126 people had mild intellectual disability (31 percent)
- 48 out of 126 people had moderate intellectual disability (38 percent)
- 39 out of 126 people had severe intellectual disability (31 percent)
Behavior
People with ARID1B-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), short attention span, impulsiveness, anger outbursts, anxiety, and poor sociability.
- 59 out of 71 people had behavioral issues (83 percent)
- 65 out of 207 people had autism or features of autism (31 percent)
- 16 out of 48 people had ADHD (33 percent)
Brain
People with ARID1B-related syndrome had seizures, most often tonic-clonic seizures. They also had lower than average muscle tone (hypotonia), a larger than average head size (macrocephaly) or smaller than average head size (microcephaly), and brain changes seen on magnetic resonance imaging (MRI).
- 56 out of 272 people had seizures (21 percent)
- 151 out of 246 people had hypotonia (61 percent)
- 60 out of 231 people had brain changes on MRI (26 percent)
Medical and physical concerns linked to ARID1B-related syndrome
Vision and hearing
People with ARID1B-related syndrome had vision impairment and eye issues, such as crossed eyes (strabismus) and changes in the optic nerve. Some people had hearing loss, including conductive hearing loss, and a few required ear tubes or hearing aids.
- 53 out of 109 people had vision impairment (49 percent)
- 48 out of 68 people had vision problems (71 percent)
- 61 out of 198 people had strabismus (31 percent)
- 60 out of 252 people had hearing loss (24 percent)
Feeding and digestion
Some people with ARID1B-related syndrome had gastrointestinal issues, such as constipation and gastroesophageal reflux disease (GERD).
- 51 out of 105 people had gastrointestinal issues (49 percent)
- 59 out of 235 people had constipation (25 percent)
- 22 out of 130 people had GERD (17 percent)
Heart
About one out of six people with ARID1B-related syndrome had heart defects, including a hole in the heart and atrial or ventricular septal defect.
- 37 out of 243 people had heart defects (15 percent)
- 15 out of 130 people had atrial septal defect (12 percent)
Other issues
Some people experienced other issues like a sideways curve of the spine, also called scoliosis, or undescended testicles in males.
- 19 out of 130 people had scoliosis (15 percent)
- 36 out of 82 males had undescended testicles (44 percent)
Tumors
In general, genetic variants that are linked to ARID1B-related syndrome are different from genetic variants that are associated with cancer. Genetic variants that are linked to ARID1B-related syndrome do not increase the risk of cancer in a person.
Adults
One research study looked at 35 adults who were 18 years and older with ARID1B-related syndrome. Many people had intellectual disability, were speaking, had behavioral challenges, were overweight, and had diagnosed eye conditions. Some had respiratory issues, seizures, urogenital defects, and issues during puberty, such as irregular menstruation, puberty delay, and reduced breast development. No adults were diagnosed with cancer.
- 20 out of 21 people had intellectual disability (95 percent)
- 20 out of 21 people were speaking (95 percent)
- 20 out of 21 people had behavioral challenges (95 percent)
- 15 out of 19 people were overweight (79 percent)
- 21 out of 21 people had diagnosed eye conditions (100 percent)
Where can I find support and resources
Coffin Siris Syndrome Foundation
The Coffin Siris Syndrome Foundation’s mission is to support, connect, and inform the Coffin-Siris Syndrome community, as well as promote and fund CSS-related research.
Simons Searchlight
Simons Searchlight is another research program sponsored and run by the Simons Foundation Autism Research Initiative, also known as SFARI. As part of the next step in your research journey, Simons Searchlight offers you the opportunity to partner with scientists and other families who have the same gene change. Simons Searchlight is a registry for more than 150 genetic changes that are associated with neurodevelopmental conditions, including autism spectrum disorder. Simons Searchlight makes it easier for researchers to access the information they need to advance research on a condition. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us Today”.
Learn more about Simons Searchlight
www.simonssearchlight.org/frequently-asked-questions
Simons Searchlight webpage with more information on ARID1B
www.simonssearchlight.org/research/what-we-study/arid1b
Simons Searchlight ARID1B Facebook community
Sources and References
- Borja, N. A., Schrier Vergano, S. A., & Tekin, M. (2023). Coffin-Siris syndrome and cancer susceptibility. Genetics in Medicine Open, 1(1), 100818. doi:10.1016/j.gimo.2023.100818
- Schmetz, A., Lüdecke, H. J., Surowy, H., Sivalingam, S., Bruel, A. L., Caumes, R., Charles, P., Chatron, N., Chrzanowska, K., … & Wieczorek, D. (2024). Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals. Human Genetics, 143(1), 71-84. doi:10.1007/s00439-023-02622-5
- van der Sluijs, P. J., Jansen, S., Vergano, S. A., Adachi-Fukuda, M., Alanay, Y., AlKindy, A., Baban, A., Bayat, A., Beck-Wödl, S., … & Santen, G. W. E. (2019). The ARID1B spectrum in 143 patients: From nonsyndromic intellectual disability to Coffin-Siris syndrome. Genetics in Medicine, 21(6), 1295-1307. doi:10.1038/s41436-018-0330-z [correction: 10.1038/s41436-018-0368-y]
- Vergano, S. A., van der Sluijs, P. J., & Santen, G. ARID1B-related disorder. 2019 May 23. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541502/
- Vasko, A., Drivas, T. G., & Schrier Vergano, S. A. (2021). Genotype-phenotype correlations in 208 individuals with Coffin-Siris syndrome. Genes (Basel), 12(6), 937. doi:10.3390/genes12060937