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 on 2024. 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.
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SMARCC2-related syndrome happens when there are changes to 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, which is caused by changes in the genes ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1.
  • Nicolaides-Baraitser syndrome, which is caused by changes in the gene SMARCA2.

Key Role

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

Symptoms

Many people who have SMARCC2-related syndrome have:

  • Developmental delay and intellectual disability
  • Speech challenges that may be severe
  • Low muscle tone
  • Feeding difficulties
  • Behavioral concerns, such as autism
  • Differences in physical appearance

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, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the genetic change.

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because SMARCC2 plays a key role in development, de novo changes in this gene can have a meaningful effect.

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

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change.

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 birth parents.

    • If neither birth parent has the same gene change 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 change in the gene.
    • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has SMARCC2-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

    • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has SMARCC2-related syndrome.
    • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has SMARCC2-related syndrome 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 2019, about 15 people in the world with changes in the SMARCC2 gene had been described in the medical literature. The first case of SMARCC2related syndrome was described in 2009. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have SMARCC2-related syndrome may look different. A study of 15 people who have the syndrome found that appearance varies and can include some but not all of these features:

  • 6 out of 15 people have extra body hair.
  • 6 out of 15 have thick eyebrows and bony ridges above the eyes.
  • 6 out of 15 have thin upper lip.
  • 5 out of 15 people have a thick lower lip.
  • 6 out of 15 people have an upturned nose.
40%
6 out of 15 people have extra body hair.
40%
6 out of 15 have thick eyebrows and bony ridges above the eyes.
40%
6 out of 15 have thin upper lip.
33%
5 out of 15 people have a thick lower lip.
40%
6 out of 15 people have an upturned nose.

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 TRIO-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

All have some intellectual disability or developmental disability.

  • 15 out of 15 people have intellectual disability or developmental disability.

Behavior 

  • 10 out of 15 have behavior issues, such as aggression, self-harm behavior, hyperactivity, hypersensitivity to touch, sleep disturbances, and obsessive and rigid behavior.

Speech

  • 13 out of 15 people have speech challenges.
  • 7 out of 15 people lack any language.
100%
15 out of 15 people have intellectual disability or developmental disability.
86%
13 out of 15 people have speech challenges.
47%
7 out of 15 people lack any language.
67%
10 out of 15 people have behavior issues, such as aggression, self-harm behavior, hyperactivity, hypersensitivity to touch, sleep disturbances, and obsessive and rigid behavior.
13%
2 out of 15 have challenges with social interactions.

Feeding and digestion issues

  • 8 out of 15 people have feeding challenges.

Muscle tone 

  • 13 out of 15 people have low muscle tone.
  • 2 out of 15 people have high tone, or overly tight or flexed muscles (high tone/spasticity).
53%
8 out of 15 have feeding challenges.
87%
13 out of 15 people have low muscle tone.
13%
2 out of 15 people have high tone, or overly tight or flexed muscles (high tone/spasticity).

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.

  • Machol K. et al. American Journal of Human Genetics, 104, 164-178, (2019). Expanding the spectrum of BAF-related disorders: de novo variants in SMARCC2 cause a syndrome with intellectual disability and developmental delay www.ncbi.nlm.nih.gov/pmc/articles/PMC6323608

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