GENE GUIDE

GRIN2B-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has GRIN2B-Related Syndrome.
a doctor sees a patient

GRIN2B-related syndrome is also called GRIN2B-related neurodevelopmental disorder, developmental and epileptic encephalopathy 27, and intellectual developmental disorder, autosomal dominant 6, with or without seizures. For this webpage, we will be using the name GRIN2B-related syndrome to encompass the wide range of variants observed in the people identified.

GRIN2B-related syndrome happens when there are changes to the GRIN2B gene. These changes can keep the gene from working as it should.

Key Role

The GRIN2B gene plays a key role in communication among brain cells. The GRIN2B gene makes part of the NMDA receptor. The gene is called GRIN2B, and the protein that makes up part of the NMDA receptor is called GluN2B.

Symptoms

Because the GRIN2B gene is important for brain activity, many people who have GRIN2B-related syndrome have: 

  • Intellectual disability
  • Global developmental delay
  • Speech delay or absent speech
  • Sleep disruption
  • Seizures
  • Delayed walking
  • Abnormal movements
  • Autism
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Lower than average muscle tone

GRIN2B-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the GRIN2B gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.

De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because GRIN2B plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that GRIN2B-related syndrome is often the result of a de novo variant in GRIN2B. Many parents who have had their genes tested do not have the GRIN2B genetic variant found in their child who has the syndrome. In some cases, GRIN2B-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

GRIN2B-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in GRIN2B they will likely have symptoms of GRIN2B-related syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the GRIN2B gene?

No parent causes their child’s GRIN2B-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.

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 GRIN2B-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 GRIN2B-related syndrome, the sibling’s risk of having a child who has GRIN2B-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing GRIN2B-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit GRIN2B-related syndrome.

As of 2024, at least 295 people with GRIN2B-related syndrome have been identified in a medical clinic. The first case of GRIN2B-related syndrome was described in 2010.

Most people who have GRIN2B-related syndrome do not look very different from others.

Scientists and doctors have only just begun to study GRIN2B-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 GRIN2B-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.

This section includes a summary of information from major published articles and the Simons Searchlight quarterly registry report. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.

Genetic variants in GRIN2B result in a gain of function, a loss of function, or a mixed function of the GluN2B protein. It is not always obvious how a change in the GRIN2B gene will affect the GluN2B protein. To better understand this requires further testing in the research laboratory.

Researchers are working to understand the differences between gain of function and loss of function GRIN2B variants. Treatment for a loss of function variant is different than treatment for a gain of function variant. Researchers think that people with certain loss of function variants tend to have more mild to moderate intellectual disability (ID), whereas people with certain missense variants may have more severe ID.

The information below includes both gain of function and loss of function variants, as there is an overlap in medical features in these groups.

Many people with GRIN2B-related syndrome had ID, and many Simons Searchlight participants reported language delays or impairment.

  • 56 out of 66 people had ID or developmental delay (85 percent)
  • 83 out of 93 people had language delays or impairment (89 percent)

The severity of ID varied among people:

  • 8 out of 54 people had mild ID (15 percent)
  • 13 out of 54 people had moderate ID (24 percent)
  • 33 out of 54 people had severe to profound ID (61 percent)
15%
8 out of 54 people had mild ID.
24%
13 out of 54 people had moderate ID.
61%
33 out of 54 people had severe to profound ID.

Behavior

Many people with GRIN2B-related syndrome had behavioral challenges, such as autism or features of autism, hyperactivity, anxiety, impulsivity, or distractibility.

  • 16 out of 61 people had autism or features of autism (26 percent)

Brain

Many people with GRIN2B-related syndrome had seizures. The age of seizure onset was between birth and 9 years old. Some people had brain changes on magnetic resonance imaging (MRI) and a smaller than average head size, or microcephaly. Brain changes on MRI included defects in cortical development.

  • 33 out of 66 people had seizures (50 percent)
  • 6 out of 47 people had brain changes seen on MRI (13 percent)
  • 11 out of 61 people had microcephaly (18 percent)
Human head showing brain outline
50%
33 out of 66 people had seizures.
13%
6 out of 47 people had brain changes seen on MRI.
18%
11 out of 61 people had microcephaly.

Mobility

People with GRIN2B-related syndrome had movement disorders and lower than average muscle tone. Movement issues included dystonia, dyskinesia, and choreiform movements.

  • 6 out of 61 people had a movement disorder (10 percent)
  • 34 out of 61 people had lower than average muscle tone (56 percent)
  • 14 out of 61 people had spasticity (23 percent)
10%
6 out of 61 people had a movement disorder.
56%
34 out of 61 people had lower than average muscle tone.
23%
14 out of 61 people had spasticity.

Feeding and digestion

Some people had feeding issues that required tube feeding. Simons Searchlight participants also reported constipation and GERD.

  • 49 out of 93 people had constipation (53 percent)
  • 38 out of 93 people had GERD (41 percent)

Vision

Some people with GRIN2B-related syndrome had cortical visual impairment.

  • 5 out of 61 people had cortical visual impairment (8 percent)

Where can I find support and resources?

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.”

Sources and references

The content in this guide comes from a published study about GRIN2B-related syndrome. Below you can find details about the study, as well as a link to the full article.

  • Platzer K. et al. Journal of Medical Genetics, 54, 460-470, (2017). GRIN2B encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects www.ncbi.nlm.nih.gov/pmc/articles/PMC5656050
  • Platzer K., & Lemke J. R. GRIN2B-related neurodevelopmental disorder. 2021 Mar 25. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501979/
  • Simons Searchlight registry update April 2024. https://cdn.simonssearchlight.org/wp-content/uploads/2024/04/16044421/GRIN2B-23Q4-24Q1.pdf
  • Xu, Y., Song, R., Perszyk, R. E., Chen, W., Kim, S., Park, K. L., Allen, J. P., Nocilla, K. A., Zhang, J., … Traynelis, S. F. (2024). De novo grin variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor. Cellular and Molecular Life Sciences, 81(1), 153. https://pubmed.ncbi.nlm.nih.gov/38538865/

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