SRF Grant to Boston Children’s Hospital for a SYNGAP1 Natural History and Biomarker Development

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What is the purpose of this grant?

To better understand SYNGAP1 development in patients, to connect SYNGAP1 variants with correlating symptom severity, and to identify a SYNGAP1 biomarker. All of these will help us design successful clinical trials.


  • This grant will allow expert analysis of the Ciitizen data (patients’ genotypes and phenotypes) as well as the EEG data from the DSC grant
  • The main goals include: creating a natural history of epilepsy in SYNGAP1 patients, developing a deeper understanding of SYNGAP1 and the development of patients’ symptoms, connecting different variants with different phenotypes, and identifying  potential SYNGAP1 biomarkers. 

In more detail:

  1. This grant aims to better describe epilepsy in SYNGAP1 patients, including information such as: age of seizure onset, types of seizures, medication, EEG data, ID, autism, etc. This information will help these researchers describe the epilepsy phenotype in SYNGAP1 patients as well as how much epilepsy variability there is among these patients. They will also see how ID and other symptoms develop along with epilepsy.
  2. Once they can learn more about epilepsy in SYNGAP1 patients, they aim to determine how the timing of epilepsy onset affects the severity of epilepsy and other symptoms, such as ID and behavioral issues. 
  3. They will use the EEG data collected from the first grant, along with Ciitizen data, etc. to hopefully determine a SYNGAP1 biomarker
  4. Lastly, they aim to correlate genotypes with phenotypes.

What does genotype and phenotype mean? 

  • Genotype refers to genes. In the case of a SYNGAP1 patient, the genotype refers to the specific variant a patient has on SYNGAP1. 
  • Phenotype refers to what can be physically observed in a patient. In the case of SYNGAP1, the phenotype refers to symptom(s) observed and their severity. 
  • When we connect genotype with phenotype severity, we can generate a deeper understanding of the gene and the disease and can better inform patient care.
  • Why is connecting genotype and phenotype important? First, this information can help inform the care of current and future patients. If we know that a specific variant often causes a certain phenotype or we know that certain medication helps other patients with similar or the same variant, we can have a better understanding of how to treat individuals and which medications are most likely to be successful for each patient.
  • For example, we have already identified 6 patients worldwide, 2 that are enrolled in Ciitizen, with a c.333del variant, and all 6 individuals are high functioning. These patients can compare medications, treatments, etc. and their experiences can help guide the care of any future patients with the same variant. 
  • If we find a pattern like this, researchers can focus on that genotype to better understand the biology behind SYNGAP1 in general and/or a specific symptom or variant. 

What’s the plan and why do we need both grants?

The DSC grant collects EEG data and this grant analyzes both the Ciitizen and EEG data.

  • The DSC grant will collect EEG data and biofluids from 20 SYNGAP1 patients.
  • In this grant, a Boston Children’s Hospital Epilepsy and Genetics team will first analyze SYNGAP1 Ciitizen data, gathered in partnership with  SRF, and develop SYNGAP1 expertise. Then, they will analyze the DSC data and hopefully identify potential SYNGAP1 biomarkers.

How much does this grant cost?


  • $238,133 total for the posdoc and various supporting staff at BCH. Consistent with SRF’s policy, no overheads are being paid with this grant.

Why is this a good investment?

This grant should result in:

  • A record of the natural history of epilepsy in SYNGAP1 patients, which is a record that describes the typical development and course of epilepsy seen in SYNGAP1 patients.
  • A deeper understanding of the general development of patients with SYNGAP1 and their symptoms over time.
  • More information about different variants and their effects on patients’ symptoms. 
  • The identification of potential SYNGAP1 biomarkers.

Why is this important?

  • When the time comes for SYNGAP1 clinical trials to begin, hopefully in the near future, we want to be ready. A solid understanding of how SYNGAP1 and its symptoms develop, connecting variants to symptoms and their severity, and having a reliable way to measure drug effectiveness (a biomarker) will all help prepare for future clinical trials and help prevent delay of potential treatments. 
  • A natural history of the epilepsy phenotype and a deeper understanding of the development of SYNGAP1 symptoms will help researchers have a general idea of what is to be expected. These guidelines can help determine if a treatment is working. For example, if a drug results in a much later onset of a certain symptom relative to the expected age, we would say that drug is helping. The goal is for this SYNGAP1 natural history record to be relatively easy to update so that our expectations either remain the same or adapt as new patients join Ciitizen. 
  • Most importantly, we need a way to measure if a drug in a clinical trial is working and we need to understand SYNGAP1 and its symptoms as well as possible. 
  • Finding out which genotypes lead to which phenotypes is also very important for future clinical trials and patient care in general. This knowledge can help researchers and doctors determine which medicine or therapy may work best for each patient.    
  • And of course it is always great when researchers are studying SYNGAP1 and becoming more familiar with the disease! 

Who can participate and how to participate?

Anyone with SYNGAP1!

  • Everyone in the Ciitizen database will have their medical information included in the analyses. Sign up for Ciitizen for free at this link
  • Anyone who would like to support this grant and SYNGAP1 research can host a fundraiser to help raise money!

Start a fundraising team and/or donate today!

The links below are helpful to better understand this opportunity: