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GENE GUIDE

SMARCC2-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated in 2026. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has SMARCC2-Related Syndrome.
a doctor sees a patient

SMARCC2-related syndrome is also called Coffin-Siris syndrome 8. For this webpage, we will be using the name SMARCC2-related syndrome to encompass the wide range of variants observed in the people identified.

SMARCC2-related syndrome happens when there are changes in the SMARCC2 gene. These changes can keep the gene from working as it should.

SMARCC2-related syndrome is similar to other syndromes that are caused by related genetic pathways. Coffin-Siris syndrome can be caused by variants in the genes ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1.

Key Role

The SMARCC2 gene plays a key role in how the brain and body develop.

Symptoms

Because the SMARCC2 gene is important for brain activity, many people who have SMARCC2-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Speech challenges that may be severe
  • Low muscle tone
  • Feeding difficulties
  • Behavioral concerns, such as autism
  • Aggression
  • Self-injury behavior
  • Hyperactivity
  • Sleep disturbances
  • Obsessive and rigid behavior

SMARCC2-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 SMARCC2 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 SMARCC2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that SMARCC2-related syndrome is often the result of a de novo variant in SMARCC2. Many parents who have had their genes tested do not have the SMARCC2 genetic variant found in their child who has the syndrome. In some cases, SMARCC2-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

SMARCC2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in SMARCC2 they will likely have symptoms of SMARCC2-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

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the SMARCC2 gene?

No parent causes their child’s SMARCC2-related syndrome. We know this because no parent has any control over the genetic 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 genetic change takes place on its own and cannot be predicted or stopped.

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 SMARCC2-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 SMARCC2-related syndrome, the sibling’s risk of having a child who has SMARCC2-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing SMARCC2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SMARCC2-related syndrome. 
  • If one biological parent has the same genetic variant causing SMARCC2-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 SMARCC2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, over 100 people in the world with changes in the SMARCC2 gene have been described in medical research. The first case of SMARCC2-related syndrome was described in 2009. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People with SMARCC2-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:

  • Thick eyebrows
  • Long eyelashes
  • Droopy eyelids
  • Upturned nose
  • Thin lip border

Scientists and doctors have only just begun to study SMARCC2-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 SMARCC2-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 a major published article. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Learning and Speech

Most people with SMARCC2-related syndrome had developmental delay and/or intellectual disability, and speech delay or impairment.

  • 49 out of 57 people had developmental delay and/or intellectual disability (86 percent)

The severity of intellectual disability (ID) varied among people:

  • 21 out of 49 people had mild ID (43 percent)
  • 28 out of 49 people had moderate to severe ID (57 percent)
86%
49 out of 57 people had developmental delay and/or intellectual disability.
43%
21 out of 49 people had mild ID.
57%
28 out of 49 people had moderate to severe ID.

Behavior

Some people with SMARCC2-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), aggressive behavior, anxiety, and oppositional behaviors.

  • 34 out of 55 people had behavioral challenges (62 percent)
  • 19 out of 56 people had features of autism (34 percent)

Brain

People with SMARCC2-related syndrome had low muscle tone (hypotonia), high muscle tone (hypertonia), seizures, sleep diagnoses, and brain changes seen on magnetic resonance imaging (MRI).

  • 38 out of 55 people had hypotonia (69 percent)
  • 13 out of 56 people had hypertonia (23 percent)
  • 17 out of 56 people had seizures (30 percent)
  • 11 out of 52 people had a sleep diagnosis (21 percent)
  • 20 out of 33 people had brain changes seen on MRI (61 percent)
Human head showing brain outline

Graphs

 
 
 
 
 

100%

80%

60%

40%

20%

0

Hypotonia
Hypertonia
Seizures
Sleep diagnosis
Brain changes seen on MRI

Vision

Some people with SMARCC2-related syndrome had vision impairment, droopy eyelids (ptosis), and crossed eyes (strabismus).

  • 17 out of 52 people had a vision impairment (33 percent)

Growth

People with SMARCC2-related syndrome had skeletal defects, were short in height, had a sideways curve of the spine (scoliosis), and had feeding difficulties or failure to thrive.

  • 17 out of 51 people had skeletal defects (33 percent)
  • 12 out of 50 people had short height (24 percent)
  • 17 out of 56 people had scoliosis (30 percent)
  • 27 out of 53 people had feeding difficulties or failure to thrive (51 percent)

Where can I find support and resources?

Coffin Siris Syndrome Foundation

Coffin-Siris Syndrome Foundation is run by volunteers affected by Coffin-Siris Syndrome (CSS). We exist to care for this community and support research that furthers the understanding of this rare syndrome.

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.”

Sources and references

The content in this guide comes from a published study about SMARCC2-related syndrome. Below you can find details about this study, as well as a link to the full article.

  • Bosch, E., Popp, B., Güse, E., Skinner, C., van der Sluijs, P. J., Maystadt, I., Pinto, A. M., Renieri, A., Bruno, L. P., … & Vasileiou, G. (2023). Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals. Genetics in Medicine, 25(11), 100950. doi:10.1016/j.gim.2023.100950
  • Li, M., Lin, J., Fei, H., Liu, J., Chen, Y., Han, X., Wang, Y., Wang, J., Hua, R., … & Li, N. (2025). Identification and functional analysis of a novel SMARCC2 splicing variant in a family with syndromic neurodevelopmental disorder. Orphanet Journal of Rare Diseases, 20(1), 48. doi:10.1186/s13023-024-03510-5
  • 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. Hum Genetics, 143(1), 71-84. doi:10.1007/s00439-023-02622-5
  • Schrier Vergano, S., Santen, G., Wieczorek, D., & Matsumoto, N. Coffin-Siris syndrome. 2025 May 15. 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/NBK131811/

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