What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Dominant Mental Retardation 5
• Syngap1 Gene Mutation linked to Intellectual Disability, Schizophrenia and Autism
• SYNGAP1 Syndrome

What is SYNGAP1-Related Non-Syndromic Intellectual Disability? (Definition/Background Information)

• SYNGAP1-Related Non-Syndromic Intellectual Disability is a condition that primarily affects the central nervous system
• It is characterized by moderate to severe intellectual disability that is usually apparent in the first few years of life. Some affected people may also experience seizures and/or autism spectrum disorder.
• This condition is caused by changes (mutations) in the SYNGAP1 gene. Almost all reported cases are due to de novo mutations; however, the condition can be passed down to future generations in an autosomal dominant manner
• The treatment of SYNGAP1-Related Non-Syndromic Intellectual Disability is based on the signs and symptoms present in each person

(Source: SYNGAP1-Related Non-Syndromic Intellectual Disability; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets SYNGAP1-Related Non-Syndromic Intellectual Disability? (Age and Sex Distribution)

• SYNGAP1-Related Non-Syndromic Intellectual Disability is a relatively common form of cognitive impairment. It accounts for about 1-2% of intellectual disability cases
• The onset of symptoms may occur in the first few years of life
• Both genders may be affected
• Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for SYNGAP1-Related Non-Syndromic Intellectual Disability? (Predisposing Factors)

• A positive family history may be an important risk factor, since SYNGAP1-Related Non-Syndromic Intellectual Disability can be inherited
• Currently, no other risk factors have been clearly identified for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of SYNGAP1-Related Non-Syndromic Intellectual Disability? (Etiology)

SYNGAP1-Related Non-Syndromic Intellectual Disability is caused by mutation(s) in the SYNGAP1 gene.

• This gene codes for SynGAP protein, which localizes to the space between nerve cells (known as synapses), and plays a role in learning and memory
• In most cases, causative SYNGAP1 mutation(s) occur sporadically, with no history of SYNGAP1-Related Non-Syndromic Intellectual Disability cases being observed in the affected individual’s family
• The condition can also be inherited in an autosomal dominant manner

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of SYNGAP1-Related Non-Syndromic Intellectual Disability?

The signs and symptoms of SYNGAP1-Related Non-Syndromic Intellectual Disability may include:

• Autistic behavior
• Developmental regression
• EEG abnormality
• Generalized hypotonia
• Global developmental delay
• Intellectual disability
• Language impairment
• Motor delay

Based on the frequency of symptoms observed, the following information may be noted:

Occasionally present symptoms in 5-29% of the cases:

• Epileptic encephalopathy
• Microcephaly
• Torticollis
• About 1%-4% of people have seizures

(Source: SYNGAP1-Related Non-Syndromic Intellectual Disability; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is SYNGAP1-Related Non-Syndromic Intellectual Disability Diagnosed?

SYNGAP1-Related Non-Syndromic Intellectual Disability is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of SYNGAP1-Related Non-Syndromic Intellectual Disability?

The complications of SYNGAP1-Related Non-Syndromic Intellectual Disability may include:

• Severe intellectual deficiency
• Trauma/injury due to epilepsy
• Status epilepticus is a seizure that lasts longer than normal. A time duration of 30-60 minutes is generally considered a minimum requirement for usage of the term Status Epilepticus, to describe the condition. It is considered a life-threatening condition and is a medical emergency
• Poor quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is SYNGAP1-Related Non-Syndromic Intellectual Disability Treated?

There is no cure for SYNGAP1-Related Non-Syndromic Intellectual Disability, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can SYNGAP1-Related Non-Syndromic Intellectual Disability be Prevented?

SYNGAP1-Related Non-Syndromic Intellectual Disability may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of SYNGAP1-Related Non-Syndromic Intellectual Disability? (Outcomes/Resolutions)

• The prognosis of SYNGAP1-Related Non-Syndromic Intellectual Disability is dependent upon the severity of the signs and symptoms and associated complications, if any
• Severe intellectual deficiency and recurrent seizures can severely affect the quality of life
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for SYNGAP1-Related Non-Syndromic Intellectual Disability:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/