SYNGAP1
What is SYNGAP1?
SYNGAP1 explained in plain language: the gene, the brain, epilepsy, development, communication and learning.
The essentials
What is SYNGAP1?
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 of the neurological issues seen in people with SYNGAP1.
- SYNGAP1 geneA variant reduces the protein produced.
- BrainSynapses mature differently.
How it shows up
- EpilepsyFrequent seizures, often difficult to control.
- DevelopmentGlobal developmental delay and reduced autonomy.
- CommunicationAbsent or limited speech; augmentative support.
- LearningIntellectual and behavioural difficulties.
What are the symptoms?
SYNGAP1 is considered a spectrum disorder since patients are not affected exactly the same way or with the same severity. The list below is a combination of the most common symptoms. People with SYNGAP1 do not always present all of these symptoms.
- 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 Behaviour 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 people with SYNGAP1 have de novo variants.
The main types of variants found are:
- Nonsense
- The variant creates a premature stop signal, producing a truncated protein.
- Missense
- The variant substitutes one amino acid, altering protein function.
- Frameshift
- The variant shifts the gene reading frame, changing the entire downstream sequence.
- Duplication
- A section of the gene is duplicated.
- Deletion
- A section of the gene is deleted.
If these symptoms sound familiar and you have not received a diagnosis, speak to your doctor about genetic testing.
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.
New SYNGAP1 patients are identified each week. We now have 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 people with SYNGAP1 improve their skills and reach milestones.
The most common therapies available are:
- Speech Therapy
- Occupational Therapy
- Physical Therapy
- Developmental Therapy
- Applied Behavioural Analysis (ABA) Therapy
People with SYNGAP1 may respond well to alternative therapies, including hippotherapy, aqua therapy, music therapy, PROMPT Therapy, and others. Every child progresses at their own pace: people with SYNGAP1 continue to make progress and reach key milestones in their own time.
Research for treatment is happening around the world with labs located in the United States, Canada, Australia, India and Europe.
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