What is Syngap?

Written in collaboration with Syngap Research Fund, USA.

Please read the following points to help you have a better understanding of Syngap and also gain some understanding of how to help your Syngap child.

Basic understanding of Syngap and how it affects your loved one

1. Basic Introduction

Syngap1 Syndrome is a rare genetic disorder caused by a mutation on the SYNGAP1 gene. It leads to several neurological issues in Syngap patients. Syngap1 was first diagnosed in 2009 by Dr Michaud at St Justine Hospital in Montreal.

2. Basic Genetics

Syngap1 Syndrome is caused by a mutation 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 mutation occurs. A mutation is a mistake that happens, similar to a typo, when the DNA is copied from cell to cell or due to environmental factors.

Fun fact: If a person typed at 60 words per minute for 8 hours a day, it would take them more than 50 years to type the entire human genome. SYNGAP gene mutation is ONE digit wrong. Just one.

A de novo mutation means the mutation is not inherited and happened very early in the process and non related to environmental factors. We could also call it the ‘bad luck’ mutation – there is nothing that the parents did or didn’t do to cause the mutation. Most, but not all, Syngap patients have de novo mutations.

The main types of mutations found are: Nonsense, Missense, Duplication and Deletion. For a basic understanding please refer to our glossary or read further here: https://ghr.nlm.nih.gov/primer/mutationsanddisorders/possiblemutations

3. Syngap1 Protein

The SYNGAP1 gene is located on Chromosome 6 and is responsible for creating the Syngap1 protein. This protein acts as a regulator in the synapses – this is where the neurones communicate with each other. A mutation of the SYNGAP1 gene leads to the gene not producing or producing less Syngap1 protein. Without the right amount of Syngap1 protein we see an increase in excitability in the synapses making it difficult for neurones to communicate effectively. This leads to many neurological issues seen in Syngap patients.

4. Symptoms

Syngap1 is considered a spectrum disorder since all 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 the most seen symptoms. Syngap patients do not always present with all of these symptoms.

  • Intellectual Disability (mild to severe)

  • Hypotonia (low muscle tone)

  • Ataxia/gait abnormalities

  • Global Development Delays

  • 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 disorder

  • High pain threshold

  • Eating problems

  • Visual Abnormalities

  • Orthopaedic abnormalities

5. The Rarity of Syngap

We currently are aware of over 500 diagnosed Syngap patients in the world but we know there are thousands more undiagnosed patients out there.

SYNGAP1 mutations should be surprisingly  common, with the incidence reported  as 1-4/10,000 individuals, or 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 Syndrome.

So few people are yet to be diagnosed for a few reasons:

  • Families receive a diagnosis like autism, intellectual disability, or epilepsy and stop their diagnostic search thinking they have reached the conclusion

  • Cost and access to genetic testing can be a barrier to getting a genetic explanation to all symptoms

  • SYNGAP1 disorder was only discovered in 2009 so all genetic testing completed before 2009 would not have shown Syngap.

6. Treatments and Cure

There is currently no cure or specific treatment for SYNGAP1. However intense therapy can help Syngap patients improve their skills and reach milestones.

The most common therapies available in Australia are Physical Therapy, Occupational Therapy, and Speech Therapy.

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

7. Current and Ongoing Syngap Research

Syngap research is happening around the world with labs located in Australia, the United States, Canada, India and Europe.  Follow Syngap Research on Facebook to keep up to date with the latest research and clinical trials.

8. Super Syngapians

As difficult as Syngap can be, Syngap patients (referred to fondly as syngapians by family members) all have their own joyful abilities. They are generally happy, loving and full of life with a contagious laugh. Most syngapians love water, music, animals and have their own super powers such as increased night vision, great sense of direction, a strong will, high pain tolerance and affectionate smiles. When they’re good there’s no one more joyful to be around!

Watch out for seizures

Over 90% of people affected by Syngap develop seizures.

If your syngapian has not been diagnosed with seizures by a neurologist, here are a few examples of what to look for, including the very typical Syngap eating seizure: https://www.youtube.com/watch?v=qxG0Rxo3Qvk

Seizures can be hard to detect since some can be very short, lasting only a split second. Most Syngap seizures are atypical absence (eye rolling, staring spell) or atonic (drop to the ground, or head drop). Some syngapians have developed a more severe form of epilepsy called Lennox Gastaut Syndrome. Most syngapians have seizures when eating, even if elsewhere they are seizure free.

Trying to get seizures under control should be a priority but there is not a ‘one size fits all’ when it comes to epilepsy treatment in our community. Some patients only need one medication, others need a combination of medicines and/or may have to go on a special diet for better results (common epilepsy diets are the Ketogenic diet or Modified Atkins).

Please work closely with your neurologist to ensure the best results are achieved for your syngapian’s seizure control.

Final words:

There is hope! To connect in with the latest research and the Australian and global Syngap community please read the ‘For Parents’ tab, contact us and get connected to the Australian and global Syngap community and be comforted that you’re not alone.