What are SYNGAP1-Related Disorders?

The image shows the SynGAP Protein (Green) in the brain. The image is credited to Yoichi Araki.

Overview

SYNGAP1-Related Disorders (SRD) are ultra-rare genetic disorders caused by a variant on the SYNGAP1 gene.

The SYNGAP1 gene is located on Chromosome 6 and is responsible for producing the SYNGAP1 protein. This protein acts as a regulator in the synapses – where neurons communicate with each other. A variant of the SYNGAP1 gene leads to the gene not producing enough SYNGAP1 protein. Without the right amount of SYNGAP1 protein we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SYNGAP1 patients.

What are the Symptoms of SRD?

Vlaskamp et. al. 2019, Neurology, Figure 6

SYNGAP1 is considered a spectrum disorder since patients are not affected exactly the same way or with the same severity. It is not known what impacts the symptoms or their severity. The list below is a combination of most seen symptoms. SYNGAP1 patients do not always present all of these symptoms.

If these symptoms sound familiar and you have not received a diagnosis, read our webpage, “Genetic Testing – What You Should Know” to learn more about genetic testing.

Intellectual Disability (mild to severe)
Hypotonia (low muscle tone)
Global Development Delay
Epilepsy (subtle eyelid flutters, brief jerks, staring seizures and drop seizures)
Sensory Processing Disorder
Gross and Fine motor skill delays
Dyspraxia (coordination disorder)
Speech delay/Apraxia (mild to severe)
Autism Spectrum Disorder
Sleep and Behavior disorders
Visual Abnormalities

What Causes SRD?

SYNGAP1-Related Disorders are caused by a variant on the SYNGAP1 gene (6p.21.32).

The human body is made of trillions of cells. Each cell contains 23 pairs of chromosomes (46 total). Each chromosome contains thousands of genes. Most genes also come in pairs and we get one copy from each parent.

The role of genes is to produce proteins. Proteins are used to regulate the body’s tissues and organs.

A gene can stop working or no longer work properly when a variant (sometimes called a mutation or alteration) occurs. A variant is a mistake that happens, similar to a typo, when the DNA is copied from cell to cell or due to environmental factors.

A de novo variant means the variant is globally present for the first time in the family and occurred very early in the reproductive process. Most SYNGAP1 patients have de novo variants. If you have access to a genetic report, this article can help you understand it better.

The main types of variants found are Nonsense, Missense, Frameshift, Duplication and Deletion. For more information on these you can visit: ghr.nlm.nih.gov/primer/mutationsanddisorders/possiblemutations.

How Many People Have SYNGAP1?

SYNGAP1 variants are surprisingly common, with the incidence reported as 6 per 100,000 or 1 per 16,000 individuals. This comprises approximately 1-2% of all Intellectual Disability (ID) cases, making it one of the most common genetic causes of ID, similar to more well known syndromes like Fragile X, Angelman and Rett.

To learn more about SYNGAP1 predicted incidence, see this detailed article by CURE SYNGAP1.

New SYNGAP1 patients are identified each week. We have now more than 1,800 SYNGAP1 patients identified worldwide. This number is too low, which means SYNGAP1 continues to be significantly under-diagnosed.

Is there a Treatment for SRD?

There is currently no cure or specific treatment for the underlying condition that causes SYNGAP1. However, intense therapy can help SYNGAP1 patients improve their skills and reach milestones.

The most common therapies available are Physical Therapy, Occupational Therapy, Speech Therapy, Developmental Therapy and Applied Behavioral Analysis (ABA) Therapy.

SYNGAP1 patients may respond well to alternative therapies, including hippotherapy, aqua therapy, music therapy, PROMPT Therapy, etc. Don’t worry if your child is taking longer than others. SYNGAP1 patients will continue to make progress and reach key milestones at their own pace.

Research for treatment is happening around the world with labs located in the United States, Canada, Australia, India and Europe.