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.
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SYNGAP1-related syndrome is also called SYNGAP1-related intellectual disability (SYNGAP1-ID) or intellectual developmental disorder, autosomal dominant 5. For this webpage, we will be using the name SYNGAP1-related syndrome to encompass the wide range of variants observed in the people identified.

SYNGAP1related syndrome happens when there are changes in 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 SYNGAP1 is important in brain activity, many people who have SYNGAP1-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Seizures
  • Autism
  • Small head size
  • Eye defects like crossed eyes
  • Excess body hair, specifically on the limbs and lower spine
  • Constipation

SYNGAP1-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 SYNGAP1 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 SYNGAP1 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

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

Autosomal dominant conditions

SYNGAP1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in SYNGAP1 they will likely have symptoms of SYNGAP1-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 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 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 SYNGAP1-related syndrome, the sibling’s risk of having a child who has SYNGAP1-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing SYNGAP1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SYNGAP1-related syndrome. 
  • If one biological parent has the same genetic variant causing SYNGAP1-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 SYNGAP1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 388 people with SYNGAP1-related syndrome have been identified in a medical clinic. The first case of SYNGAP1-related syndrome was described in 2015.

Do people who have SYNGAP1related syndrome look different?

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

  • Almond-shaped opening of the eyes
  • Slight open-mouthed appearance
  • 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 and learning

Most children who have SYNGAP1-related syndrome showed some degree of intellectual disability, ranging from mild to severe. They required special educational support. Almost all children who have SYNGAP1-related syndrome had speech delay. The average age of speaking the first word was 24 months. But, some people were non-verbal.

  • 147 out of 147 people had developmental delay and intellectual disability (100 percent)

Behavior

Some people who have SYNGAP1-related syndrome had autism or features of autism, challenging behaviors, anxiety, and sleep problems. Some of the behavioral issues were aggressive behaviors, self-injurious behavior, and irritability.

  • 100 out of 147 people had features of autism (68 percent)
  • 100 out of 147 people had behavioral issues (68 percent)
  • 35 out of 147 people had an anxiety disorder (24 percent)
  • 90 out of 147 people had sleeping issues (61 percent)
68%
100 out of 147 people had features of autism.
68%
100 out of 147 people had behavioral issues.
24%
35 out of 147 people had an anxiety disorder.
61%
90 out of 147 people had sleeping issues.

Brain

Aside from ID, the second most common feature people with SYNGAP1-related syndrome had was epilepsy. Common seizure types included generalized seizures, absence or atypical absence seizures, atonic seizures, reflex seizures, and tonic-clonic seizures.

  • 123 out of 147 people had epilepsy (84 percent)

Mobility

Most had low muscle tone, also called hypotonia. Low muscle tone can cause delays in developmental milestones, such as sitting and walking, as well as a wide-based or unsteady walk. Average age of walking was 20 months.

  • 69 out of 147 people had ataxia or abnormal gait (47 percent)

Feeding and digestion

About one-half of people with SYNGAP1-related syndrome had feeding issues. Some people needed a feeding tube. Feeding difficulties included swallowing issues, oral aversion, and failure to thrive.

  • 69 out of 147 people had feeding difficulties (47 percent)

Eyes

Some people with SYNGAP1-related syndrome had crossed eyes.

  • 32 out of 147 people had crossed eyes (22 percent)

Adults

A small number of people with SYNGAP1-related syndrome over the age of 18 years old have been described in medical research. The oldest person was 65 years old. Most people were dependent on caregivers for activities of daily living, and about one-half could walk independently.

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
  • Wiltrout, K., Brimble, E., & Poduri, A. (2024). Comprehensive phenotypes of patients with SYNGAP1-related disorder reveals high rates of epilepsy and autism. Epilepsia, 65(5), 1428-1438. https://pubmed.ncbi.nlm.nih.gov/38470175/
  • Rong, M., Benke, T., Zulfiqar Ali, Q., Aledo-Serrano, Á., Bayat, A., Rossi, A., Devinsky, O., Qaiser, F., Ali, A. S., … Andrade, D. M. (2023). Adult phenotype of SYNGAP1-DEE. Neurology Genetics, 9(6), e200105. https://pubmed.ncbi.nlm.nih.gov/38045990/

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