GRIN-related Disorders

Disease Overview

Summary  

GRIN-related disorders are a group of rare genetic disorders that share similar symptoms, mainly affecting brain development and function (neurodevelopmental issues).1-4 They are considered a type of encephalopathy, which refers to disorders in which brain function is affected.   

People with GRIN-related disorders may have a wide range of symptoms. These can include mild to severe intellectual disability, delays in reaching developmental milestones (developmental delays), movement disorders, a variety of seizure types, and the features commonly associated with autism spectrum disorder.1-4 The specific symptoms and the severity of GRIN-related disorders can vary greatly from one person to another, even among individuals with the same disorder. It is important to note that affected individuals will not develop all the symptoms discussed in this report.   

Currently there is no cure for any of the GRIN-related disorders. Treatment focuses on improving the symptoms that the affected person has.  

Introduction  

GRIN-related disorders are caused by changes (variations) in certain genes. These genes include the GRIN1, GRIN2A, GRIN2B, and GRIN2D genes.5 These genes contain instructions for creating (encoding) proteins that play a role in the health and function of the central nervous system, which includes the brain and spinal cord. Other GRIN genes exist (e.g., GRIN2C, GRIN3A, GRIN3B), but their associations with specific diseases are less well established.6   

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Synonyms

• GRINpathies
• GRIN-related Encephalopathy
• GRIN-related Neurodevelopmental Disorder
• GRIN-related complex neurodevelopmental disorder

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Subdivisions

GRIN1-related disorders  

Synonyms:   

• GRIN1-related neurodevelopmental disorder (GRIN1-NDD)  

Subtypes:   

• Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (OMIM 614254)  

• Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (OMIM 617820)  

• Developmental and epileptic encephalopathy 101 (OMIM 619814)  

GRIN2A-related disorder  

Synonyms:   

• GRIN2A-Related Disorders  

• Epilepsy, focal, with speech disorder and with or without impaired intellectual development (OMIM 245570)  

GRIN2B-related disorder  

Synonyms:   

• GRIN2B-Related Neurodevelopmental Disorder  

• GRIN2B Encephalopathy  

• GRIN2B-related developmental delay, intellectual disability, and autism spectrum disorder (Orphanet 589547)  

Subtypes:  

• Intellectual developmental disorder, autosomal dominant 6, with or without seizures (OMIM 613970)   

• Developmental and epileptic encephalopathy-27 (DEE27) also known as Early infantile epileptic encephalopathy, 27; EIEE27 (OMIM 616139) 

Note: OMIM 613970 and OMIM 616139 describe different features within the same GRIN2B-related neurodevelopmental disorder, rather than separate genetic subtypes.  

 GRIN2D-related disorder  

Synonyms:   

• GRIN2D-Related Developmental and Epileptic Encephalopathy  

• Developmental and epileptic encephalopathy 46 (OMIM 617162)  

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Signs & Symptoms

Because only a limited number of individuals with GRIN-related disorders have been identified, and because many subtypes are still poorly understood, NORD cannot yet provide detailed descriptions of every form of the disorder. As more affected individuals are diagnosed and studied, researchers expect to gain a clearer clinical understanding of the different subtypes and their features. Most common signs and symptoms include:   

• Developmental delays  

• • Developmental delays occur when a child does not reach expected milestones, such as sitting up, crawling, walking independently, or speaking, at the age they would normally be expected to do so 

• Intellectual disability  

• • Intellectual disability can range from mild to severe and varies greatly between individuals 

• • Affected individuals may display a variety of learning disabilities during childhood ²  

• • Intellectual disability and developmental delays have been reported in most people with GRIN1-related disorders1,7  

• • Intelligence may be unaffected, mildly affected, or moderately to severely affected in children with GRIN2A-related disorders²  

• • All reported people with GRIN2B- and GRIN2D-related disorders have some degree of intellectual disability and developmental delays 3,4  

• Seizures  

• • Seizures can occur in individuals with any GRIN-related disorders.1-4, 9, 10  

• • Seizures are caused by abnormal electrical activity in the brain and may affect movement, sensation, consciousness, personality, and behavior.  

• • Seizure onset generally occurs between birth and the first decade of life.1-4  

• • Seizure frequency varies widely and may range from multiple seizures per day to only a few seizures per year.  

• • Affected individuals may experience different types of seizures throughout their lives.  

• Microcephaly, an abnormally small head circumference  

• Low muscle tone (hypotonia)  

• Increased muscle stiffness and tightness that worsens with movement (spasticity)1-4  

• • Spasticity may be associated with involuntary muscle spasms.  

• • If left untreated, spasticity can result in permanent tightening of muscles, tendons, and ligaments (contractures).¹¹  

• Movement disorders  

• • Movement disorders may occur and can include:1-4  

• • • Dystonia, uncontrollable, sometimes painful muscle contractions  

• • • Chorea, random, continuous involuntary movements while awake that may affect the entire body  

• • • Dyskinesia, involuntary, uncontrolled movements including spasms, jerks, and writhing  

• • • Athetosis, abnormal muscular contractions causing slow, irregular movements  

• • • Oculogyric crisis, characterized by sudden upward deviation of the eyes  

• • • Movement disorders may impair fine motor skills, making it difficult to perform tasks requiring precise hand and finger movements  

• • • Daily activities such as grooming, dressing, and writing may be affected  

• Neuropsychiatric and behavioral features1-4  

• • Anxiety disorders  

• • Mood disorders  

• • Sleep disorders  

• • Attention deficit/hyperactivity disorder (ADHD)  

• • Autism spectrum disorders features, such as:¹²  

• • • Avoiding eye contact  

• • • Not responding to their name  

• • • Disliking physical touch  

• • • Speaking with an unusual tone or rhythm  

• • • Difficulty with social interaction or communication  

• • • Repetitive, non-purposeful movements, including hand flapping and head banging (stereotypical movements)  

• Vision abnormalities  

• • Cortical visual impairment, a condition in which the brain is unable to properly interpret visual signals due to dysfunction in the visual processing centers that leads to difficulties: 3,4, 13 

• • Responding to visual stimuli  

• • Recognizing faces or objects  

• • Understanding what they are seeing  

• • Reaching for objects they can see  

• Speech and language difficulties that may include:1-4  

• • Mild speech impairment  

• • Slurred or slowed speech (dysarthria)  

• • Difficulty with understanding and/or expressing language (aphasia)  

• Feeding and gastrointestinal problems, including:4  

• • Difficulty swallowing (dysphagia)  

• • Backflow of stomach contents into the esophagus (gastroesophageal reflux)  

• • Recurrent vomiting  

• • Constipation  

Additional gene-specific conditions include:   

GRIN1-related disorders:   

•  Some children may have short stature (shorter than expected for age and sex)¹   

• Some may develop scoliosis, an abnormal side-to-side curvature of the spine¹  

• Brain anomalies detected by brain imaging include abnormal brain surface development with too many small folds (polymicrogyria), enlarged fluid-filled spaces/cavities (ventricles or extra fluid around the brain), reduced white matter, a thin or underdeveloped corpus callosum (the bridge between the brain’s halves), changes in deeper structures like the basal ganglia or hippocampus, and sometimes overall smaller brain volume or white-matter changes.1  

GRIN2A-related disorders:   

• Some reports suggest an increased risk of schizophrenia, a psychiatric condition affecting thought, mood, and behavior2, 14    

• • Symptoms may include hallucinations, delusions, and disorganized thinking or behavior   

• Some individuals develop Landau–Kleffner syndrome, a specific epilepsy syndrome characterized by loss of language comprehension and verbal expression.2, 15, 16   

GRIN2B-related disorders:   

• Infants may be at increased risk of developing West syndrome, a form of epilepsy characterized by:2, 5   

• • An abnormal EEG pattern known as hypsarrhythmia   

• • Cognitive dysfunction   

• • Spasms that may range from severe jackknife movements involving the entire body to subtle shoulder twitches or changes in eye movements¹⁷   

• • Brain malformations (detected in brain imaging) such as polymicrogyria, a thin or underdeveloped corpus callosum, changes in deeper brain structures, and in some cases, overall reduced brain size, and/or an underdeveloped (brain atrophy).3   

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Causes

The GRIN-related disorders are caused by changes (variants) in specific genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a variation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced.18 Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.  

GRIN1-related disorders are caused by changes in the GRIN1 gene; GRIN2A-related disorders are caused by changes in the GRIN2A gene, GRIN2B-related disorders are caused by changes in the GRIN2B gene; and GRIN2D-related disorders are caused by changes in GRIN2D gene.19  

The GRIN genes contain instructions for creating proteins that are essential for the normal structure and function of N-methyl-D-aspartate receptors (NMDA receptors).5,6 A receptor is a specialized structure on a cell or group of cells that detects and responds to specific signals. NMDA receptors are important for the proper development and function of the brain.1 NMDA receptors are a type of ion channel. Ion channels connect nerve cells (neurons) by allowing electrically charged particles, called ions, to pass through tiny openings (pores) in the cell membrane. This movement of ions allows nerve cells to communicate electrically with one another.  

NMDA receptors respond to a neurotransmitter called glutamate. Neurotransmitters are chemical messengers that transmit chemical messages between nerve cells (neurons) and are essential for communication within the central nervous system, which includes the brain and spinal cord.  

Under normal conditions, glutamate binds to the NMDA receptor, causing the ion channel to open. This allows ions to flow into the cell and enables communication between nerve cells (neurons). This process is critical for normal brain development and for cognitive functions such as learning, memory, and other thinking skills.1, 9 

The two more common variants that can affect the GRIN genes are: 

• Gain-of-function variants, in which the NMDA receptor is overactive and out of balance5  

• Loss-of-function variants, in which the NMDA receptor does not open properly and is underactive.16, 20  

Different GRIN gene variants can be associated with different symptoms and severity of these disorders.5, 8  

Inheritance 

Most GRIN-related disorders are inherited in an autosomal dominant manner.  

Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. When a parent has a GRIN-related disorder, the chance of passing the gene variant from an affected parent to a child is 50% with each pregnancy. The risk is the same for males and females.  

GRIN1-, GRIN2B-, and GRIN2D-related disorders typically result from a de novo gene variant, which occurs for the first time in the affected person, and it is not inherited.1, 3-4  

About half of the reported individuals with GRIN2A-related disorder have a de novo variant (a new genetic change present for the first time and not inherited), and the other half are inherited from a parent. In some families, the parent’s symptoms may be very different or much milder than the child’s, such as subtle speech or learning difficulties.I  In rare cases a parent may carry the change in only some of their cells (mosaicism) and appear unaffected. Because of this, genetic testing of both parents is recommended even when there is no obvious family history. If a parent carries the genetic change, each sibling of the affected child has a 50% chance of inheriting it; if not, the risk is low but slightly higher than average.2 

Although uncommon, some individuals with a GRIN1-related disorder inherit the condition in an autosomal recessive manner.1, 7 Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.  

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Affected populations

GRIN-related disorders affect both males and females. The exact number of people affected is unknown. Rare disorders like GRIN-related disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population.   

As of 2025, fewer than 100 individuals with a GRIN1-related disorder have been reported in the medical literature.1 More than 400 individuals with GRIN2A-related disorder have been reported in the medical literature.2 GRIN2B-related disorders may be the most common (have the highest incidence).21 According to the GRIN2B Foundation, more than 750 people worldwide are known to have a GRIN2B-related disorder.22 Fewer than 30 individuals with GRIN2D-related disorders have been reported in the medical literature.4   

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Disorders with Similar Symptoms

There are many disorders that can cause signs and symptoms similar to those seen in people with GRIN-related disorders. These include better known disorders such as cerebral palsy, and a wide variety of other genetic neurodevelopmental disorders. The signs and symptoms of GRIN-related disorders alone are not specific enough to distinguish the disorder from many of these other, similar disorders.1,3-4 Some affected individuals have symptoms that are consistent with those for individuals with autism spectrum disorder.  

Epilepsy is a general term for a group of neurological disorders characterized by recurrent seizures associated with abnormal electrical activity in the brain. Seizures may involve loss of consciousness, convulsions, spasms, sensory confusion, or disturbances in the autonomic nervous system (affecting functions such as breathing or heart rate).  

There are many different types of epilepsy, and the exact cause is often unknown. Epilepsy can also occur as part of larger syndromes. Types of epilepsy or disorders associated with epilepsy that can have similar symptoms with GRIN-related disorders include Rett syndrome, Angelman syndrome, Landau-Kleffner syndrome, Dravet syndrome, and neuronal ceroid lipofuscinoses.  

Because GRIN-related disorders overlap with many neurologic and genetic conditions, genetic testing is  needed to confirm the diagnosis. 

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Diagnosis

A diagnosis of a GRIN-related disorder may be suspected based on a person’s symptoms, especially seizures, developmental delays, intellectual disability, hypotonia, and features of autism spectrum disorder, along with a detailed patient and family history, and a thorough clinical evaluation including specific tests.1-4 

A diagnosis can be confirmed through molecular genetic testing, which can detect changes (variants) in the specific genes known to cause GRIN-related disorders.1-4 Molecular genetic testing is available only as a diagnostic service at specialized laboratories. To perform the test, a doctor will collect a blood sample or a buccal swab (collecting DNA or cells from the inner cheek). Testing may include targeted epilepsy or neurodevelopmental gene panels and/or whole exome sequencing (WES) WES is a molecular genetic testing method that examines the portion of a person’s genetic material called the exome, which includes all genes that contain instructions for creating proteins (protein-encoding genes). WES can detect disease-causing variants in the GRIN genes, as well as variants in other genes that may cause similar symptoms.  

Additional tests may be used to support the diagnosis or better understand how the brain is affected. These tests may include:  

• Electroencephalogram (EEG), a test that records the brain’s electrical activity and can help identify seizures or abnormal brain wave patterns1-4, 23 

• Magnetic resonance imaging (MRI), a test that uses magnetic fields and radio waves to create detailed, cross-sectional images of particular organs and bodily tissues, including the brain  

Some people with GRIN-related disorders may have abnormal development (malformation) of the cerebral cortex, which is the outer layer of a part of the brain responsible for higher-level functions (the cerebrum).1,3 On MRI, this malformation may appear as too many small folds or ridges in the brain (polymicrogyria),24  corpus callosum hypoplasia, cerebral atrophy and abnormalities in other cerebral structures.2 

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Standard Therapies

Treatment 

There are currently no curative treatments for GRIN-related disorders. Treatment is mainly supportive and focuses on managing symptoms that are apparent in each person. Treatment plans are highly individualized and depend on factors such as the specific symptoms, severity of the disorder, an individual’s age and overall health and tolerance to certain medications or procedures.  

Treatment may require the coordinated efforts of a team of specialists.2, 4, 9 Depending on individual factors such as age of onset, specific symptoms, and rate of progression, consultations with various specialists may be necessary, including pediatricians, specialists in the diagnosis and treatment of developmental delays and disabilities in children (developmental pediatricians), specialists in the diagnosis and treatment of neurological disorders (neurologists), specialists in the diagnosing and treatment of communication and swallowing disorders (speech language pathologists), specialists in the diagnosis and treatment of eye disorders (ophthalmologists), specialists in the diagnosis and treatment of the gastrointestinal tract (gastroenterologists), and other healthcare professionals.1-4  

Following diagnosis, a comprehensive developmental assessment should be performed, and appropriate occupational, physical, speech, and feeding therapies should be started.1-4 Periodic reassessments and adjustments of services are recommended for all children. Most therapies are supportive and are designed to improve quality of life, maximize function, and reduce complications.2 Supportive therapies can include: 1-4 

• Physical therapy to maintain strength and movement  

• Occupational therapy to manage symptoms, maintain function, and improve quality of life 

• Walking aids (such as canes, walkers, or crutches) to help with coordination and balance 

Seizures may be treated with a variety of anti-seizure medications.1-4 These medications may be effective in treating seizures associated with GRIN-related disorders, but no specific medication has been demonstrated as being specifically effective in these disorders. Additionally, children or adults who initially improved with anti-seizure medications can develop medication resistance later on, meaning the treatment becomes less effective over time.  

Because speech impairment and communication difficulties are common, strong consideration should be given to early training with alternative and augmentative communication devices, which can help children express thoughts, wants, needs, and ideas.1-4  

Children may benefit from interventions used in autism spectrum disorder such as applied behavioral analysis (ABA) therapy targeted to the strengths and weaknesses of each child. A developmental pediatrician can help with management of behavioral issues and medication considerations, while more serious, aggressive behaviors may be helped by a pediatric psychiatrist.  

Standardized therapy with an experienced psychiatrist can be helpful with behavioral issues. Various medications have been used to treat affected individuals, but none have been demonstrated to be effective specifically for people with GRIN-related disorders.  

In people with limited communication, potential medical issues that cause discomfort, such as severe constipation, should be carefully evaluated, as these issues might adversely impact behavior. 

Speech and swallowing difficulties may be treated with certain medications or with special therapy. In severe cases of feeding difficulty, affected individuals may have a small, thin tube inserted into the stomach through a small cut in the abdomen (gastrostomy tube) to ensure they receive sufficient nutrients.1-4 

Abnormal muscle tone (e.g., hypotonia, spasticity, or dystonia) may be treated with medications such as baclofen, tizanidine, and Botox®.1-4  

In individuals with vision abnormalities, early intervention with vision therapy may support visual development.  

Early intervention services during infancy and toddlerhood (before the age of three) are especially important to help children reach their potential. These may include therapy services, special education, and social services.1-4  

An Individualized Family Support Plan (IFSP) may be developed to guide the early intervention process for infants and toddlers with disabilities. An individual education plan (IEP) or a 504 plan may be developed to ensure that the child receives access to an equal education through accommodations in their learning environment.1-4 Such planning is individualized because intellectual disability and learning needs vary widely among affected individuals.  

In United States, families can consider enrolling in their state’s Developmental Disabilities Administration, a U.S. program that helps individuals with intellectual disabilities access services and supports. Eligibility requirements vary by U.S. state.1-4  

Genetic counseling can help affected individuals and their families understand inheritance patterns, recurrence risks, and family planning options.1-4 Ongoing psychosocial supportive services for the entire family are also important.1-4 

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Clinical Trials and Studies

A medication called radiprodil is being studied to treat individuals with GRIN-related disorders caused by gain-of-function variants. Radiprodil targets certain NMDA receptors to help to reduce their overactivity, which may help restore more normal receptor function. Early studies suggest that the medication is well-tolerated and may reduce seizure activity in some affected individuals. Radiprodil is investigational and is not yet approved for clinical use. More research is needed to determine its long-term safety and effectiveness.25-27  

Some people with GRIN-related disorders with specific GRIN genes variants s (e.g., loss-of-function or null variants)28 have been treated with a non-essential amino acid called L-serine. L-serine acts as a co-agonist at the NMDA receptor and may help to enhance the activity of the receptor. Initial studies have shown that some individuals demonstrated improvement in behavior, development, and, sometimes, seizure frequency.2, 28-29 More research is necessary to determine the long-term safety and effectiveness of L-serine for the treatment of certain individuals with GRIN-related disorders.  

Memantine is a medication that affects NMDA receptors, which are the same brain receptors involved in GRIN-related disorders. Because of this, memantine has been tried in some people with GRIN gene changes, especially when the genetic variant causes the receptor to be overactive (called a gain-of-function variant). In some individuals, memantine has led to improvements in seizures, attention, behavior, or development, but responses are highly variable and not guaranteed. In others, there may be little benefit or no change, and in rare cases symptoms can worsen. Memantine is not helpful and may be inappropriate for GRIN variants that cause the receptor to be underactive (loss-of-function). 30 

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. 

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: 

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected] 

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/ 

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/ 

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/ 

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References

1. Platzer K, Lemke JR. GRIN1-Related Neurodevelopmental Disorder. In: GeneReviews® [Internet]. Adams MP, Feldman J, Mirzaa GA, eds., et al. Seattle (WA): University of Washington, Seattle; Updated April 1, 2021. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK542807/ 
2. Strehlow V, Myers KA, Morgan AT, Scheffer IE, Lemke JR. GRIN2A-Related Disorders. In: GeneReviews® [Internet]. Adams MP, Feldman J, Mirzaa GA, eds., et al. Seattle (WA): University of Washington, Seattle; Updated July 4, 2024. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK385627/ 
3. Platzer K, Lemke JR. GRIN2B-Related Neurodevelopmental Disorder. In: GeneReviews® [Internet]. Adams MP, Feldman J, Mirzaa GA, eds., et al. Seattle (WA): University of Washington, Seattle; Updated March 25, 2021. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK501979/ 
4. Platzer K, Krey I, Lemke JR. GRIN2D-Related Developmental and Epileptic Encephalopathy. In: GeneReviews® [Internet]. Adams MP, Feldman J, Mirzaa GA, eds., et al. Seattle (WA): University of Washington, Seattle; Updated July 28, 2022. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK582335/ 
5. Cha JH, Kim JM, Yun HJ, et al. Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders. NPJ Genom Med. 2025;10(1):40. https://pubmed.ncbi.nlm.nih.gov/40374652/ 
6. Benke TA, Park K, Frey I, et al. Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs. Neuropharmacology. 2021;199:108805. https://pmc.ncbi.nlm.nih.gov/articles/PMC8525401/ 
7. Lemke JR, Gieder K, Helbig KL, et al. Delineating the GRIN1 phenotypic spectrum. Neurology. 2016;86(23):2171-2178. https://pmc.ncbi.nlm.nih.gov/articles/PMC4898312/ 
8. Myers SJ, Yuan H, Kang JQ, Tan FCK, Traynelis SF, Low CM. Distinct roles of GRIN2A and GRIN2B variants in neurological conditions. F1000Res. 2019;8:F1000. https://pubmed.ncbi.nlm.nih.gov/31807283/ 
9. Di Muro E, Palumbo P, Carella M, et al. Long-Term Phenotypic Evolution in GRIN2A-Related Disorders: Electroclinical and Genetic Insights from Two Families with Extended Follow-Up. Genes (Basel). 2025;16(3):323. https://pmc.ncbi.nlm.nih.gov/articles/PMC11941913/ 
10. Korinek M, Candelas Serra M, Abdel Rahman F, et al. Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology. Physiol Res. 2024;73(Suppl 1):S413-S434. https://pmc.ncbi.nlm.nih.gov/articles/PMC11412357/ 
11. Spasticity. Yale Medicine. Accessed: December 10, 2025. https://www.yalemedicine.org/conditions/spasticity 
12. Autism Spectrum Disorder. Mayo Clinic. Updated: May 22, 2025. Accessed: December 10, 2025. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928 
13. Cortical Vision Impairment. National Eye Institute. Updated: December 4, 2024. Accessed: December 10, 2025. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/cerebral-visual-impairment-cvi 
14. Schizophrenia. National Institute of Mental Health. Updated: December 2024. Accessed: December 10, 2025. https://www.nimh.nih.gov/health/topics/schizophrenia 
15. Ebrahim AK, Makhlooq JJ, Busehail MY. Landau-Kleffner Syndrome Can Herald the Diagnosis of GRIN2A Gene Mutation. Case Rep Pediatr. 2025;2025:8869587. https://pubmed.ncbi.nlm.nih.gov/40727434/ 
16. Santos-Gomez A, Miguez-Cabello F, Garcia-Recio A, et al. Disease-associated GRIN protein truncating variants trigger NMDA receptor loss-of-function. Hum Mol Genet. 2021;29(24):3859-3871. https://pubmed.ncbi.nlm.nih.gov/33043365/ 
17. West Syndrome. National Organization for Rare Disorders. Updated: April 23, 2019. Accessed: December 10, 2025. https://rarediseases.org/rare-diseases/west-syndrome/ 
18. Gene. National Human Genome Research Institute. Updated: December 10, 2025. Accessed December 10, 2025. https://www.genome.gov/genetics-glossary/Gene 
19. Online Mendelian Inheritance in Man (OMIM). Updated December 9, 2025. Accessed on December 10, 2025. https://www.omim.org/ 
20. Dong B, Yue Y, Dong H, Wang Y. N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders. Front Mol Neurosci. 2023;16: 1174738. https://pubmed.ncbi.nlm.nih.gov/37396784/ 
21. Lemke JR. Predicting incidences of neurodevelopmental disorders. Brain. 2020;143:1046-1048. https://academic.oup.com/brain/article/143/4/1046/5823474 
22. Common Questions. GRIN2B Foundation. Accessed December 10, 2025. https://grin2b.com/common-questions/ 
23. Strehlow V, Rieubland C, Gallati S, et al. Compound-heterozygous GRIN2A null variants associated with severe developmental and epileptic encephalopathy. Epilepsia. 2022;63(10):e132-e137. https://pubmed.ncbi.nlm.nih.gov/35983985/ 
24. Fry AE, Fawcett KA, Zelnick N, et al. De novo mutations in GRIN1 cause extensive bilateral polymicrogyria. Brain. 2018;141(3):698-712. https://pmc.ncbi.nlm.nih.gov/articles/PMC5837214/ 
25. CheckRare. Breakthrough Therapy Designation GRIN-Related Neurodevelopmental Disorders Treatment [Video]. YouTube. https://www.youtube.com/watch?v=6wOWkvfvsSo  Accessed: December 10, 2025.  
26. CheckRare. Topline Results of the Honeycomb Trial for GRIN-related Neurodevelopmental Disorders [Video]. YouTube. https://www.youtube.com/watch?v=xtlrhmI3FdU Accessed: December 10, 2025.  
27. Bertocchi I, Cifarelli L, Oberto A, et al. Radiprodil, a selective GluN2B negative allosteric modulator, rescues audiogenic seizures in mice carrying the GluN2A(N615S) mutation. Br J Pharmacol. 2024;181(12):1886-1894. https://pubmed.ncbi.nlm.nih.gov/38529699/ 
28. Krey I, von Spiczak S, Johannesen KM, et al. L-Serine treatment is associated with improvements in behavior, EEG, and Seizure frequency in individuals with GRIN-related disorders due to null variants. Neurotherapeutics. 2022;19:334-341. https://pubmed.ncbi.nlm.nih.gov/34997442/ 
29. Julia-Palacios N, Olivella M, Sigatullina-Bondarenko M, et al. L-serine treatment in patients with GRIN-related encephalopathy: a phase 2A, non-randomized study. Brain. 2024;147(5):1653-1666. https://pubmed.ncbi.nlm.nih.gov/38380699/ 
30. Karnstedt M, Perszyk RE, Myers SJ, et al. Memantine treatment in individuals with GRIN gain-of-function variants is associated with improvements in behavior, development, and seizure frequency. Epilepsia. Published online January 5, 2026. doi:10.1002/epi.70090 

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Programs & Resources

• Assistance Programs
• Patient Organizations
• More Information

RareCare^® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Learn more about Patient Assistance Programs >

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