GRIN2D-Related Syndrome

GRIN2D-related syndrome happens when there are changes in the GRIN2D 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 GRIN2D-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 GRIN2D-related syndrome, the sibling’s risk of having a child who has GRIN2D-related syndrome depends on the sibling’s genes and their parents’ genes.

• If neither parent has the same genetic variant causing GRIN2D-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit GRIN2D-related syndrome.

As of 2025, more than 24 people with GRIN2D-related syndrome have been identified in medical research.

Most people who have GRIN2D-related disorder do not look different from others.

Scientists and doctors have only just begun to study GRIN2D-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 GRIN2D-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.

Speech and learning

All people with GRIN2D-related syndrome had global developmental delay and/or intellectual disabilities, from mild to profound.

• 23 out of 23 people had global developmental delay and/or intellectual disability (100 percent)

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

• 1 out of 23 people had mild ID (4 percent)
• 1 out of 23 people had moderate ID (4 percent)
• 13 out of 23 people had severe/profound ID (57 percent)
• 8 out of 23 people had ID severity that was not defined (35 percent)

Many people with GRIN2D-related syndrome had speech issues. Some were able to speak only a few words and some were non-verbal.

• 2 out of 22 people were able to speak a few words (9 percent)
• 8 out of 22 people were non-verbal (36 percent)

Behavior

Some people with GRIN2D-related syndrome had behavioral issues such as autism.

• 4 out of 22 people had autism or features of autism (18 percent)

Brain

People with GRIN2D-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 had more than one seizure type. There was no common medication that worked for all people. The average age of seizure onset was 11 months old. Five people had developmental regression and seizures.

• 13 out of 23 people had hypotonia (57 percent)
• 21 out of 24 people had seizures (88 percent)
• 8 out of 17 people had changes seen on MRI (47 percent)

Mobility

People with GRIN2D-related syndrome had a movement disorder, such as jerky movements or involuntary movements (chorea), and/or unusual tightness or stiffness of the muscles (spasticity). Sometimes people had a loss of muscle coordination and balance (ataxia).

• 8 out of 22 people had a movement disorder (36 percent)
• 4 out of 22 people had spasticity (18 percent)
• 3 out of 22 people had ataxia (14 percent)

Feeding and digestion

About 1 in 3 people had feeding challenges, and one person had a feeding tube.

• 7 out of 23 people had feeding difficulties (30 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 GRIN2D – www.simonssearchlight.org/research/what-we-study/grin2d
• Simons Searchlight GRIN2D Facebook community – https://www.facebook.com/groups/grin2d