Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

SYNGAP1-Related Intellectual Disability

Sometimes just called SYNGAP1 or SYNGAP1 syndrome.

What is SYNGAP1-Related Intellectual Disability?

• SYNGAP1-related intellectual disability is a developmental encephalopathy that impacts the central nervous system
• The condition is named after the gene which is altered in the disorder and leads to the appearance of symptoms
• Diagnosis takes place via a genetic test
• Though poorly understood and generally rare, SYNGAP1 occurs with frequency rates similar to more well-known disorders such as Rett syndrome, Angelman syndrome, or fragile X syndrome
  • The incidence rate is estimated at 6.1 per 100,000 births
  • However, only just over 1,000 cases have been identified. This means that SYNGAP1-related intellectual disability is heavily underdiagnosed

How Do You Get It?

• SYNGAP1-related intellectual disability is caused by genetic mutations impacting the SYNGAP1 gene
• This gene is responsible for the production of a protein called SynGAP, which is important for the function of the brain’s nerve cells.
• These mutations prevent the production of functional SynGAP protein
  • The lack of functioning SynGAP can cause the cell synapses to develop to quickly
• In the vast majority of cases, SYNGAP1 occurs as a result of a de novo, or spontaneous, mutation and is not inherited

What Are the Symptoms?

• The symptoms of SYNGAP1-related intellectual disability occur in a spectrum
  • This means that severity of symptoms can vary greatly, and all patients are not impacted in the same way
• Symptoms of SYNGAP1 include:
  • Hypotonia (low muscle tone)
  • Global developmental delay
  • Sensory processing disorder
  • Intellectual disability, which can range from mild to severe
  • Epilepsy
    • Seizure types that are found in SYNGAP1 include:
      • Tonic-clonic seizures
      • Atonic seizures
      • Myoclonic jerks
      • Eyelid myoclonia
      • Myoclonic absences
  • Vision abnormalities
  • Motor skill delays
  • Sleep and behavior disorders
  • Dyspraxia (coordination disorders)
  • Autism

How Is It Treated?

• There is no cure or disease-altering therapy for SYNGAP1-related intellectual disability
• Antiepileptic drugs, ketogenic diet, and Vagus nerve stimulation can be used to control seizures
  • However, about half of patients have seizures that are resistant to treatment
• A feeding tube may be needed in patients that have trouble eating
• Patients may also use supportive devices to improve mobility and communication
• Other supportive therapies that are used in SYNGAP1 can include:
  • Physical therapy
  • Occupational therapy
  • Aquatic therapy
  • Music therapy
  • Speech therapy
  • Applied behavior analysis

Where Can I Learn More???

• Learn more about this disease from the SynGAP Research Fund.
• Check out our cornerstone on this disease here.