GENE GUIDE

SYNGAP1-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 SYNGAP1-Related Syndrome.
a doctor sees a patient

SYNGAP1-related syndrome happens when there are changes to the SYNGAP1 gene. These changes can keep the gene from working as it should.

Key Role

The SYNGAP1 gene plays a key role in the development and function of the brain. It makes a protein that helps to control brain activity. When one copy of the SYNGAP1 gene is not working properly, the brain may become overactive.

Symptoms

Because the SYNGAP1 gene controls brain activity, changes in this gene can be linked to seizures and other challenges. SYNGAP1-related syndrome can affect the development of communication, social, and learning skills. Many people who have SYNGAP1-related syndrome have:

  • Developmental delay, or intellectual disability, or both
  • Hyperactivity and sleep problems
  • Autism or features of autism
  • Seizures
  • Joint and spine issues
  • Low muscle tone
  • Constipation

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the SYNGAP1 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 gene 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 SYNGAP1 plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that SYNGAP1-related syndrome is often the result of a de novo change in SYNGAP1. Many parents who have had their genes tested do not have the SYNGAP1 gene change found in their child. In some cases, SYNGAP1-related syndrome happens because the gene change was passed down from a parent.

Our genes are arranged in long threads called chromosomes. The SYNGAP1 gene is located on chromosome 6. Some people who are missing parts of chromosome 6, including the entire SYNGAP1 gene, have symptoms similar to people who have changes in the SYNGAP1 gene.

Child who has genetic change in SYNGAP1 gene

Genetic change occurs in egg or sperm after fertilization
Child with de novo genetic change in autism gene

Why does my child have a change in the SYNGAP1 gene?

No parent causes their child’s SYNGAP1-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.

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 SYNGAP1-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 SYNGAP1-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 SYNGAP1-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 SYNGAP1-related syndrome is 50 percent.

For a person who has SYNGAP1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2017, doctors had found about 85 people in the world with changes in the SYNGAP1 gene. The first case of SYNGAP1-related syndrome was described in 2015. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

Do people who have SYNGAP1related syndrome look different?

People who have SYNGAP1-related syndrome do not look very different. Appearance can vary and can include some but not all of these features:

  • Broad nasal bridge
  • Long nose
  • Full lower lip

Scientists and doctors have only just begun to study SYNGAP1-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 SYNGAP1-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.

Speech

Almost all children who have SYNGAP1-related syndrome have speech delay. Children are often late to start talking and may have limited vocabulary.

Learning

Most children who have SYNGAP1-related syndrome show some degree of intellectual disability, ranging from mild to severe. They need special educational support.

Behavior

Some people who have SYNGAP1-related syndrome have aggressive or challenging behaviors and sleep problems.

A study of 10 people who have SYNGAP1-related syndrome found these symptoms:

Brain and muscle tone

Low muscle tone, also called hypotonia, which can cause delays in developmental milestones, such as sitting and walking, as well as a wide-based or unsteady walk.

  • 8 out of 10 people had low muscle tone.
  • 7 out of 10 people had epilepsy.

Feeding and digestion issues

  • 5 out of 10 people had constipation

Eyes

  • 3 out of 10 people had crossed eyes, also called strabismus.

Joints

  • 2 out of 10 people had problems with the hip socket, also called hip dysplasia.

Facial features

Some people who have SYNGAP1-related syndrome have distinct facial features, such as a broad nasal bridge, a long nose, and a full lower lip.

80%
80 percent of people had low muscle tone.
70%
7 out of 10 people had epilepsy.
50%
5 out of 10 people had constipation.
30%
3 out of 10 people had crossed eyes, also called strabismus.
20%
2 out of 10 people had problems with the hip socket, also called hip dysplasia.

Where can I find support and resources?

SYNGAP1 Foundation

The SYNGAP1 Foundation stands as a pioneering force, holding the distinction of being the world’s first organization dedicated to propelling research initiatives for the betterment of patients and families affected by SYNGAP1-related Disorders and related neurological conditions that overlap.

SynGAP Research Fund Foundation

SRF is a 501(c)(3) public charity incorporated in 2018. Their mission is to improve the quality of life of SYNGAP1 patients through the research and development of treatments, therapies and support systems.

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 published studies about SYNGAP1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Parker MJ. et al. American Journal of Medical Genetics Part A, 167A, 2231-2237, (2015). De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability www.ncbi.nlm.nih.gov/pubmed/26079862
  • Mignot C. et al. Journal of Medical Genetics, 53, 511-522, (2016). Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy www.ncbi.nlm.nih.gov/pubmed/26989088
  • Prchalova D. et al. BMC Medical Genetics, 18, 62, (2017). Analysis of 31-year-old patient with SYNGAP1 gene defect points to the importance of variants in broader splice regions and reveals the developmental trajectory of SYNGAP1-associated phenotype www.ncbi.nlm.nih.gov/pubmed/28576131

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