By: Clare Logan
SYNGAP1 Gene and Epilepsy
What is the SYNGAP1 Gene?
The SYNGAP1 gene, located on chromosome 6, provides instructions for producing a
protein called SYNGAP. This protein is highly concentrated in the brain and is essential for
healthy brain development, learning, and memory. It helps nerve cells, or neurons, communicate
with each other through connections called synapses. When there is a change, or pathogenic
variant, in the SYNGAP1 gene, the protein may not function properly. This disruption often
affects brain signaling, which may result in developmental delays, intellectual disability, epilepsy
(seizures), and sometimes autism spectrum disorder or other behavioral challenges.
SYNGAP1-Related Epilepsy
Epilepsy is one of the most common features of SYNGAP1-related conditions. Seizures
typically begin between 4 months and 7 years of age, with the average onset around 2–3 years. In
some cases, seizures may begin in infancy or later in childhood. Common seizure types
associated with SYNGAP1 include:
● Absence seizures – brief staring spells or sudden lapses in consciousness.
● Eyelid Myoclonia – quick eyelid flickers, sometimes followed by temporary loss of
muscle control.
● Myoclonic-atonic seizures – sudden “drop attacks” causing a person to go limp or fall
due to a temporary loss of muscle tone.
● Tonic-clonic seizures – sudden loss of consciousness with jerking movements of the
body, commonly known as “grand mal” seizures.
Before a genetic diagnosis, individuals may be diagnosed with other epileptic conditions, such as
Doose syndrome or Jeavons syndrome. Some individuals may also receive a diagnosis of
Lennox–Gastaut syndrome if specific electroencephalogram (EEG) patterns are observed.
In about one-quarter of those with SYNGAP1-related epilepsy, seizures are triggered by
eating or chewing. Other triggers can include flashing lights, visual patterns, or certain sounds.
Across those with SYNGAP1-related epilepsy, seizure frequency can vary, with some individuals
experiencing more than 100 seizures per day during active periods. As for anti-seizure
medication (ASM), about half respond to at least one, while the rest are often drug-resistant.
Currently, no medication directly targets the underlying cause of SYNGAP1-related seizures.
Research and Treatment
At present, there is no cure for SYNGAP1-related epilepsy. Treatment methods often
focus on controlling seizures, managing behavioral symptoms, and supporting overall
development. Common approaches include ASMs, dietary therapies such as the Modified Atkins
Diet, and vagus nerve stimulation. Supportive therapies, such as physical, occupational, and
speech therapy, can enhance motor and communication skills. Behavioral interventions, such as
applied behavior analysis, which are often used for autism, may also be beneficial. It is important
to note, however, that treatment is typically highly individualized and requires a multidisciplinary
team.
Research is still ongoing to better understand how SYNGAP1 changes, or variants, affect
brain function, particularly since many changes appear spontaneously rather than being inherited.
Scientists are exploring therapies that target the underlying brain signaling problems, including
treatments that may regulate specific brain receptors. While still in the research phase, these
approaches hold promise for more targeted and individualized treatments in the future.
Resources:
Epilepsy Foundation. (n.d.). SYNGAP1-related epilepsy. Epilepsy
Foundation.https://www.epilepsy.com/causes/genetic/syngap1-related-epilepsy
Holder, J. L., Hamdan, F. F., & Michaud, J. L. (2019). SYNGAP1-related intellectual
disability. In M. P. Adam, J. Feldman, G. M. Mirzaa, et al. (Eds.), GeneReviews®. University of
Washington, Seattle.https://www.ncbi.nlm.nih.gov/books/NBK537721/
Layne, C., Diaz, D., Malaya, C., Suter, B., & Holder, J. (2025). Gait Kinematics of
Individuals with SYNGAP1-Related Disorder Compared with Age-Matched
Neurotypical Individuals. Applied Sciences, 15(15), 8267.
Syngap Research Fund. (n.d.). SYNGAP1 & epilepsy. Syngap Research
Fund.https://curesyngap1.org/syngap1-epilepsy
