GRIN2A-Related Syndrome

GRIN2A-related syndrome happens when there are changes to the GRIN2A gene. These changes can keep the gene from working as it should.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.

The risk of having another child who has GRIN2A-related syndrome depends on the genes of both biological parents.

• If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant.
• If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free brother or sister of someone who has GRIN2A-related syndrome, the sibling’s risk of having a child who has GRIN2A-related syndrome depends on the sibling’s genes and their parents’ genes.

• If neither parent has the same genetic variant causing GRIN2A-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit GRIN2A-related syndrome.

As of 2025, about 400 people with GRIN2A-related syndrome have been identified in a medical clinic.

People who have GRIN2A-related syndrome do not look different from others.

Scientists and doctors have only just begun to study GRIN2A-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

• • Physical exams and brain studies
  • Genetics consults
  • Development and behavior studies
  • Other issues, as needed

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

• • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for GRIN2A-related syndrome should begin as early as possible, ideally before a child begins school.

If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: www.epilepsy.com/learn/types-seizures.

People with a GRIN2A loss of function variant tend to have:

• Mild medical features
• Speech disorders and/or seizures
• Mild or average intellectual disability 

People with a GRIN2A gain of function variant tend to have:

• More medical features
• intellectual disability and seizures

Speech and learning

Many people with GRIN2A-related syndrome had global developmental delay and/or intellectual disabilities, from mild to profound.

• 111 out of 177 people had global developmental delay and/or intellectual disability (63 percent)

The severity of intellectual disability (ID) varied among people:

• 33 out of 74 people had mild ID (45 percent)
• 17 out of 74 people had moderate ID (23 percent)
• 8 out of 74 people had severe ID (11 percent)
• 16 out of 74 people had profound ID (22 percent)

Most people had speech and/or language disorders, including speech delays, regression, or inability to speak due to damage of the brain (aphasia).

• 129 out of 140 people had speech and/or language disorders (92 percent)

The severity of language disorders varied among people:

• 55 out of 115 people had moderate speech delay (48 percent)
• 18 out of 115 people were non-verbal (16 percent)
• 26 out of 115 people had speech delays (23 percent)
• 16 out of 115 people had speech regression or aphasia (14 percent)

Brain

People with GRIN2A-related syndrome had low muscle tone (hypotonia), seizures, and/or changes seen on magnetic resonance imaging (MRI).

Seizure types included focal, generalized spasms, and epileptic spasms. Some people had seizures that were resistant to medications. People with null variants tended to have a later seizure onset (about 4 and a half years old) than people with missense variants (about 3 years old).

• 40 out of 139 people had hypotonia (29 percent)
• 192 out of 219 people had seizures (88 percent)
• 12 out of 85 people had changes seen on MRI (14 percent)

Mobility

About 1 in 4 people with GRIN2A-related syndrome had a movement disorder, such as involuntary muscle contractions (dystonia), involuntary movements (chorea), and loss of muscle coordination and balance (ataxia).

• 19 out of 72 people had a movement disorder (26 percent)

CureGRIN

CureGRIN is a foundation founded and run by parents who are committed to improving the lives of people living with GRI Disorders.

• https://curegrin.org/

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

• Learn more about Simons Searchlight – www.simonssearchlight.org/frequently-asked-questions
• Simons Searchlight webpage with more information on GRIN2A – www.simonssearchlight.org/research/what-we-study/grin2a
• Simons Searchlight GRIN2B Facebook community – https://www.facebook.com/groups/grin2a