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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>GRIN2B-Related Neurodevelopmental Disorder - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="GRIN2B-Related Neurodevelopmental Disorder">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2021/03/25">
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<meta name="citation_author" content="Konrad Platzer">
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<meta name="citation_author" content="Johannes R Lemke">
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<meta name="citation_keywords" content="GRIN2B Encephalopathy">
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<meta name="citation_keywords" content="GRIN2B Encephalopathy">
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<meta name="citation_keywords" content="Glutamate receptor ionotropic, NMDA 2B">
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<meta name="citation_keywords" content="GRIN2B">
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<meta name="citation_keywords" content="GRIN2B-Related Neurodevelopmental Disorder">
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<meta name="DC.Title" content="GRIN2B-Related Neurodevelopmental Disorder">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Konrad Platzer">
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<meta name="DC.Contributor" content="Johannes R Lemke">
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<meta name="DC.Date" content="2021/03/25">
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<meta name="description" content="GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported.">
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<meta name="og:description" content="GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK501979_"><span class="title" itemprop="name"><i>GRIN2B</i>-Related Neurodevelopmental Disorder</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>GRIN2B</i> Encephalopathy</div><p class="contribs">Platzer K, Lemke JR.</p><p class="fm-aai"><a href="#_NBK501979_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 23 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="grin2b.Summary" itemprop="description"><h2 id="_grin2b_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>GRIN2B</i>-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with <i>GRIN2B</i>-related neurodevelopmental disorder have been reported.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of a <i>GRIN2B</i>-related neurodevelopmental disorder is established in a proband by identification of either a heterozygous pathogenic variant or exon or whole-gene deletion of <i>GRIN2B</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> DD/ID, muscle tone abnormalities (spasticity, hypotonia, and feeding difficulties), epilepsy, ASD/behavioral issues, movement disorders, and/or cortical visual impairment are treated as per standard practice.</p><p><i>Surveillance:</i> Of clinical manifestations as clinically indicated.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>GRIN2B</i>-related neurodevelopmental disorder is inherited in an autosomal dominant manner. All probands reported to date with a <i>GRIN2B</i>-related neurodevelopmental disorder whose parents have undergone molecular genetic testing have the disorder as a result of a <i>de novo GRIN2B</i> pathogenic variant or deletion. If the proband represents a simplex case (i.e., the only affected family member) and the <i>GRIN2B</i> pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental mosaicism. Given this risk, prenatal testing and preimplantation genetic testing may be considered.</p></div></div><div id="grin2b.Diagnosis"><h2 id="_grin2b_Diagnosis_">Diagnosis</h2><p>Formal diagnostic criteria for <i>GRIN2B</i>-related neurodevelopmental disorder have not been established.</p><div id="grin2b.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>GRIN2B</i>-related neurodevelopmental disorder <b>should be considered</b> in individuals with the following clinical and/or brain MRI findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Mild-to-profound developmental delay (DD) or intellectual disability (ID); AND</div></li><li class="half_rhythm"><div>Any of the following features presenting in infancy or childhood:</div><ul><li class="half_rhythm"><div>Epilepsy</div></li><li class="half_rhythm"><div>Autism spectrum disorder / behavioral issues</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Muscle tone abnormalities such as hypotonia (occasionally associated with feeding difficulties) and spasticity</div></li><li class="half_rhythm"><div>Dystonic, dyskinetic, or choreiform movement disorder</div></li><li class="half_rhythm"><div>Cortical visual impairment</div></li></ul></li></ul><p><b>Brain MRI findings.</b> MRI reveals a malformation of cortical development (MCD) consisting of diffuse cortical dysplasia including polymicrogyria, hypoplastic corpus callosum, enlarged/dysplastic basal ganglia, and hippocampal dysplasia. The MCD can also resemble the tubulinopathies spectrum (see <a href="/books/n/gene/tubulin-ov/?report=reader">Tubulinopathies Overview</a>).</p></div><div id="grin2b.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of a <i>GRIN2B</i>-related neurodevelopmental disorder <b>is established</b> in a proband by identification of either a heterozygous pathogenic (or likely pathogenic) variant or exon or whole-gene deletion of <i>GRIN2B</i> on molecular genetic testing (see <a href="/books/NBK501979/table/grin2b.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobgrin2bTmoleculargenetictestingused">Table 1</a>).</p><p>Note: (1) Larger contiguous-gene deletions including but not limited to <i>GRIN2B</i> are not discussed in this <i>GeneReview</i>. (2) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bibr" href="#grin2b.REF.richards.2015.405" rid="grin2b.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (3) Identification of a heterozygous <i>GRIN2B</i> variant of uncertain significance does not establish or rule out the diagnosis.</p><p><b>Molecular genetic testing approaches</b> can include use of a multigene panel, chromosomal microarray analysis, and/or more comprehensive genomic testing.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotypes of many disorders with intellectual disability overlap, most children with <i>GRIN2B</i>-related neurodevelopmental disorder are diagnosed by genomic testing. Note: Single-gene testing (sequence analysis of <i>GRIN2B</i>, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>An intellectual disability multigene panel</b> that includes <i>GRIN2B</i> and other genes of interest (see <a href="#grin2b.Differential_Diagnosis">Differential Diagnosis</a>) typically provides the best opportunity to identify the genetic cause of the condition while limiting identification of pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For <i>GRIN2B</i>-related disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK501979/table/grin2b.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobgrin2bTmoleculargenetictestingused">Table 1</a>).</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Chromosomal microarray analysis (CMA)</b> uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>GRIN2B</i>) that cannot be detected by sequence analysis.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bTmoleculargenetictestingused"><a href="/books/NBK501979/table/grin2b.T.molecular_genetic_testing_used/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobgrin2bTmoleculargenetictestingused"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.T.molecular_genetic_testing_used"><a href="/books/NBK501979/table/grin2b.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobgrin2bTmoleculargenetictestingused">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>GRIN2B</i>-Related Neurodevelopmental Disorder </p></div></div></div></div><div id="grin2b.Clinical_Characteristics"><h2 id="_grin2b_Clinical_Characteristics_">Clinical Characteristics</h2><div id="grin2b.Clinical_Description"><h3>Clinical Description</h3><p><i>GRIN2B</i>-related neurodevelopmental disorder is characterized in all affected individuals by mild to profound developmental delay / intellectual disability (DD/ID). Epilepsy (seen in 51%) and autism spectrum disorder (ASD) and autistic-like behaviors (26%) are common. Other infantile- or childhood-onset findings include microcephaly; muscle tone abnormalities (hypotonia, spasticity); dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. To date, fewer than 100 individuals with <i>GRIN2B</i>-related neurodevelopmental disorder have been reported in cohorts of individuals with DD/ID/ASD, early-onset epilepsy, and malformations of cortical development (MCD).</p><p>Unless otherwise noted, the information in this section is based on extended data of <a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al [2017]</a>. Detailed clinical assessment was available for 61 affected individuals, with specification of ID in 54. Brain MRI was performed in 47 individuals.</p><div id="grin2b.DDID"><h4>DD/ID</h4><p>The degree of DD/ID can be severe or profound (61%, 33/54), moderate (24%, 13/54), or mild (15%, 8/54) using standard assessments of psychomotor development or IQ testing.</p><p>Signs of developmental regression have been noted in four children (7%, 4/61), one of whom had transient regression of language skills at age six years with improvement beginning at age eight years and another who had recurrent periods of global regression starting at age three years. No detailed information is available for the other two children.</p></div><div id="grin2b.Muscle_Tone_Abnormalities"><h4>Muscle Tone Abnormalities</h4><p>Hypotonia has been reported in more than half the affected individuals (56%, 34/61). Five (15% of those with muscular hypotonia) required tube feeding. All five of these individuals had severe ID.</p><p>Spasticity was seen in 14 (23%) of 61 individuals, all with severe ID.</p></div><div id="grin2b.Epilepsy"><h4>Epilepsy</h4><p>Epilepsy is present in 31 (51%) of 61 of individuals and characterized by the following.</p><p>
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<b>Features</b>
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</p><ul><li class="half_rhythm"><div>Onset is from birth to age nine years.</div></li><li class="half_rhythm"><div>Seizure frequency ranges from multiple episodes per day to a few seizures per year.</div></li><li class="half_rhythm"><div>Seizures are refractory to anti-seizure medication in approximately half of individuals treated.</div></li></ul><p>
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<b>Seizure types</b>
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</p><ul><li class="half_rhythm"><div>Seizures may be generalized (58%, 18/31) and/or focal (48%, 15/31) and/or epileptic spasms (35%, 11/31) with some individuals displaying multiple seizure types over time.</div></li><li class="half_rhythm"><div>EEG patterns comprise generalized, focal, and multifocal epileptiform activity and/or hypsarrhythmia.</div></li></ul><p><b>Syndromes.</b> Most children with epileptic spasms also show hypsarrhythmia or hypsarrhythmia-like EEG patterns and fulfill diagnostic criteria for West syndrome.</p></div><div id="grin2b.ASD"><h4>ASD</h4><p>Autistic features were seen in 16 (26%) of 61 individuals. In addition, in one study of the behavioral phenotype of five individuals with <i>GRIN2B-</i>related neurodevelopmental disorder without ASD, the authors observed hyperactivity, impulsivity, distractibility, stereotypies, short attention span, sleeping problems, and social behavior that is friendly but lacking boundaries [<a class="bibr" href="#grin2b.REF.freunscht.2013.20" rid="grin2b.REF.freunscht.2013.20">Freunscht et al 2013</a>].</p></div><div id="grin2b.Other"><h4>Other</h4><p>Microcephaly occurred in 11 (18%) of 61 individuals; all 11 had severe ID. Three of these also had an MCD.</p><p>Movement disorders (10%, 6/61) included involuntary dystonic, dyskinetic, and/or choreiform movements.</p><p>Cortical visual impairment (CVI) (8%, 5/61) has been reported in four affected individuals: three also had an MCD, and the fourth, who had a normal brain MRI, was identified in a cohort of individuals with ID and CVI [<a class="bibr" href="#grin2b.REF.bosch.2016.660" rid="grin2b.REF.bosch.2016.660">Bosch et al 2016</a>].</p><p>Note: A report of an individual with approximately 50% mosaicism for a <i>GRIN2B</i> pathogenic missense variant in blood (no other tissues were tested) did not provide sufficient clinical information to allow comparison of the phenotype with individuals with a heterozygous germline pathogenic variant [<a class="bibr" href="#grin2b.REF.stosser.2018.403" rid="grin2b.REF.stosser.2018.403">Stosser et al 2018</a>].</p></div><div id="grin2b.Brain_Imaging"><h4>Brain Imaging</h4><p>A malformation of cortical development (MCD) has been seen in six (13%) of 47 individuals; the diffuse cortical dysplasia was consistent with that of polymicrogyria. Cortical findings included a mixture of large and small gyri separated by shallow sulci (<a class="figpopup" href="/books/NBK501979/figure/grin2b.F1/?report=objectonly" target="object" rid-figpopup="figgrin2bF1" rid-ob="figobgrin2bF1">Figure 1</a>). The gray-white border appeared smooth.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figgrin2bF1" co-legend-rid="figlgndgrin2bF1"><a href="/books/NBK501979/figure/grin2b.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figgrin2bF1" rid-ob="figobgrin2bF1"><img class="small-thumb" src="/books/NBK501979/bin/grin2b-Image001.gif" src-large="/books/NBK501979/bin/grin2b-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndgrin2bF1"><h4 id="grin2b.F1"><a href="/books/NBK501979/figure/grin2b.F1/?report=objectonly" target="object" rid-ob="figobgrin2bF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">MRI of individuals with malformation of cortical development A-D: patient 1; E-H: patient 2; I-L: patient 3; M-P: patient 4; Q-T: patient 5; U-X: patient 6; AA-DD: normal control</p></div></div><p>Other findings included the following:</p><ul><li class="half_rhythm"><div>Hypoplastic corpus callosum of varying degrees</div></li><li class="half_rhythm"><div>Enlarged and mildly dysplastic basal ganglia</div></li><li class="half_rhythm"><div>Hippocampal dysplasia with thick leaves and open hilus</div></li><li class="half_rhythm"><div>Enlarged tecta</div></li><li class="half_rhythm"><div>Absent septum pellucidum</div></li></ul><p>The malformation of cortical development is also consistent with that of tubulinopathies (see <a href="/books/n/gene/tubulin-ov/?report=reader">Tubulinopathies Overview</a>). The identified individuals with MCD display a very similar degree of severity, and there are no reports of affected individuals with less pronounced malformations of cortical development.</p><p>Generalized cerebral volume loss indicating cerebral atrophy was seen in four other individuals (9%, 4/47).</p></div></div><div id="grin2b.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Variant class and intellectual outcome show a significant correlation: heterozygotes for a <i>GRIN2B</i> pathogenic variant resulting in a null allele (e.g., nonsense or frameshift variants, deletion involving whole exons or the entire gene, translocation and inversion disrupting <i>GRIN2B</i>) tended to display mild or moderate ID, while heterozygotes for pathogenic missense variants displayed severe ID (Fisher's exact test, p=0.0079) [<a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>].</p><p>Missense variants in <i>GRIN2B</i> that cause a malformation of cortical development are located in transmembrane domain M3, in the ligand-binding domain S2, and in the linker between S2 and the transmembrane domain M4, a finding consistent with <i>GRIN1</i> variants causing an MCD [<a class="bibr" href="#grin2b.REF.fry.2018.698" rid="grin2b.REF.fry.2018.698">Fry et al 2018</a>] (see <a href="/books/n/gene/grin1-ndd/?report=reader"><i>GRIN1</i>-Related Neurodevelopmental Disorder</a>).</p></div><div id="grin2b.Penetrance"><h3>Penetrance</h3><p>Penetrance of <i>GRIN2B</i>-related neurodevelopmental disorder is thought to be 100%.</p></div><div id="grin2b.Prevalence"><h3>Prevalence</h3><p>The prevalence of <i>GRIN2B</i>-related neurodevelopmental disorder in the general population is unknown. To date, fewer than 100 individuals have been reported.</p><p>The prevalence of <i>GRIN2B</i>-related neurodevelopmental disorder among individuals with neurodevelopmental disorders and/or childhood-onset epilepsy is around 0.2% [<a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>].</p></div></div><div id="grin2b.Genetically_Related_Allelic_Disor"><h2 id="_grin2b_Genetically_Related_Allelic_Disor_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>GRIN2B.</i></p></div><div id="grin2b.Differential_Diagnosis"><h2 id="_grin2b_Differential_Diagnosis_">Differential Diagnosis</h2><p>Phenotypic features associated with heterozygous <i>GRIN2B</i> pathogenic variants are not sufficient to diagnose <i>GRIN2B</i>-related neurodevelopmental disorder.</p><p>All genes known to be associated with ID, early-onset epileptic encephalopathy, and malformations of cortical development (especially diffuse polymicrogyria and tubulinopathies) should be included in the differential diagnosis of <i>GRIN2B</i>-related neurodevelopmental disorder (see <a href="/books/NBK501979/table/grin2b.T.genes_to_consider_in_the_differ/?report=objectonly" target="object" rid-ob="figobgrin2bTgenestoconsiderinthediffer">Table 2</a>) as individuals with <i>GRIN2B</i>-related neurodevelopment disorder can present with a combination of clinically unspecific phenotypes such as DD/ID/ASD and/or epilepsy. The underlying genetic causes of these phenotypes comprise a very heterogeneous group of disorders, as is the case with tubulinopathies, polymicrogyria, and their differential diagnoses.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bTgenestoconsiderinthediffer"><a href="/books/NBK501979/table/grin2b.T.genes_to_consider_in_the_differ/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobgrin2bTgenestoconsiderinthediffer"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.T.genes_to_consider_in_the_differ"><a href="/books/NBK501979/table/grin2b.T.genes_to_consider_in_the_differ/?report=objectonly" target="object" rid-ob="figobgrin2bTgenestoconsiderinthediffer">Table 2. </a></h4><p class="float-caption no_bottom_margin">Genes to Consider in the Differential Diagnosis of <i>GRIN2B</i>-Related Neurodevelopmental Disorder </p></div></div></div><div id="grin2b.Management"><h2 id="_grin2b_Management_">Management</h2><div id="grin2b.Evaluations_Following_Initial_Dia"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>GRIN2B</i>-related neurodevelopmental disorder, the evaluations summarized in <a href="/books/NBK501979/table/grin2b.T.recommended_evaluations_followi/?report=objectonly" target="object" rid-ob="figobgrin2bTrecommendedevaluationsfollowi">Table 3</a> (if not performed as part of the evaluation that led to diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bTrecommendedevaluationsfollowi"><a href="/books/NBK501979/table/grin2b.T.recommended_evaluations_followi/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobgrin2bTrecommendedevaluationsfollowi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.T.recommended_evaluations_followi"><a href="/books/NBK501979/table/grin2b.T.recommended_evaluations_followi/?report=objectonly" target="object" rid-ob="figobgrin2bTrecommendedevaluationsfollowi">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder </p></div></div></div><div id="grin2b.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bTtreatmentofmanifestationsin"><a href="/books/NBK501979/table/grin2b.T.treatment_of_manifestations_in/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobgrin2bTtreatmentofmanifestationsin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.T.treatment_of_manifestations_in"><a href="/books/NBK501979/table/grin2b.T.treatment_of_manifestations_in/?report=objectonly" target="object" rid-ob="figobgrin2bTtreatmentofmanifestationsin">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder </p></div></div><div id="grin2b.Developmental_Delay__Intellectual"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the United States, early intervention is a federally funded program available in all states.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p>
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<b>Ages 5-21 years</b>
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</p><ul><li class="half_rhythm"><div>In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.</div></li><li class="half_rhythm"><div>Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.</div></li></ul><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.</p><p>Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</p><p>In the US:</p><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="grin2b.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
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<b>Gross motor dysfunction</b>
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</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility.</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction.</b> Assuming that the individual is safe to eat by mouth, feeding therapy, typically from an occupational or speech therapist is recommended for affected individuals who have difficulty feeding as a result of poor oral motor control.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties.</p></div><div id="grin2b.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications (e.g., medication used to treat attention-deficit/hyperactivity disorder) when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="grin2b.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bTrecommendedsurveillanceforin"><a href="/books/NBK501979/table/grin2b.T.recommended_surveillance_for_in/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobgrin2bTrecommendedsurveillanceforin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.T.recommended_surveillance_for_in"><a href="/books/NBK501979/table/grin2b.T.recommended_surveillance_for_in/?report=objectonly" target="object" rid-ob="figobgrin2bTrecommendedsurveillanceforin">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder </p></div></div></div><div id="grin2b.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#grin2b.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="grin2b.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>In vitro studies on oocytes of <i>Xenopus laevis</i> suggest a beneficial treatment response of pathogenic missense <i>GRIN2B</i> gain-of-function variants to blockers of the N-methyl D-aspartate receptor (e.g., memantine, radiprodil) [<a class="bibr" href="#grin2b.REF.lemke.2014.147" rid="grin2b.REF.lemke.2014.147">Lemke et al 2014</a>, <a class="bibr" href="#grin2b.REF.mullier.2017.322" rid="grin2b.REF.mullier.2017.322">Mullier et al 2017</a>, <a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>]. However, a significant clinical benefit from treatment with such compounds has not yet been demonstrated [<a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>].</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="grin2b.Genetic_Counseling"><h2 id="_grin2b_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="grin2b.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>GRIN2B</i>-related neurodevelopmental disorders are inherited in an autosomal dominant manner.</p></div><div id="grin2b.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>To date all probands with a <i>GRIN2B</i>-related neurodevelopmental disorder whose parents have undergone molecular genetic testing have the disorder as a result of a <i>de novo GRIN2B</i> pathogenic variant or <i>GRIN2B</i> exon or whole-gene deletion.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband with an apparent <i>de novo</i> genetic alteration.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the pathogenic variant most likely occurred <i>de novo</i> in the proband. Another possible explanation is that the proband inherited a genetic alteration from a parent with germline mosaicism. Although parental germline mosaicism has not been reported to date, molecular genetic tests sensitive enough to detect low-level germline mosaicism (e.g., allele-specific PCR, next-generation sequencing methods) may be considered.</div></li><li class="half_rhythm"><div>Theoretically, if the parent is the individual in whom the <i>GRIN2B</i> genetic alteration first occurred, the parent may have somatic mosaicism for the variant and may be mildly/minimally affected [<a class="bibr" href="#grin2b.REF.stosser.2018.403" rid="grin2b.REF.stosser.2018.403">Stosser et al 2018</a>].</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>The risk to the sibs of the proband depends on the genetic status of the proband's parents: if the proband represents a simplex case (i.e., the only affected family member) and the <i>GRIN2B</i> pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental mosaicism [<a class="bibr" href="#grin2b.REF.rahbari.2016.126" rid="grin2b.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>In a study assessing mosaicism in the apparently asymptomatic parents of children with developmental and epileptic encephalopathy, the frequency of parental somatic and (inferred) germline mosaicism was 10% [<a class="bibr" href="#grin2b.REF.myers.2018.1646" rid="grin2b.REF.myers.2018.1646">Myers et al 2018</a>].</div></li></ul><p><b>Offspring of a proband.</b> Individuals with a <i>GRIN2B</i>-related neurodevelopmental disorder are not known to reproduce.</p><p><b>Other family members.</b> Given that all probands with a <i>GRIN2B</i>-related neurodevelopmental disorder reported to date have the disorder as a result of a <i>de novo</i> genetic alteration, the risk to other family members is presumed to be low.</p></div><div id="grin2b.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to parents of affected individuals.</div></li></ul></div><div id="grin2b.Prenatal_Testing_and_Preimplantat"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Risk to future pregnancies is presumed to be low, as the proband most likely has a <i>de novo</i>
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<i>GRIN2B</i> pathogenic variant or deletion of <i>GRIN2B</i>. However, based on the theoretic possibility of parental mosaicism (reported to be 10% in one study on apparently asymptomatic parents of children with developmental and epileptic encephalopathy [<a class="bibr" href="#grin2b.REF.myers.2018.1646" rid="grin2b.REF.myers.2018.1646">Myers et al 2018</a>]), the recurrence risk to sibs is estimated to be 1% [<a class="bibr" href="#grin2b.REF.rahbari.2016.126" rid="grin2b.REF.rahbari.2016.126">Rahbari et al 2016</a>]. Given this risk, prenatal testing and preimplantation genetic testing may be considered.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="grin2b.Resources"><h2 id="_grin2b_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>CureGRIN Foundation</b>
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</div><div><b>Phone:</b> 303-881-3425</div><div>
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<a href="https://curegrin.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">curegrin.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>GRIN2B Foundation</b>
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</div><div><b>Email:</b> info@grin2b.com</div><div>
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<a href="http://grin2b.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.grin2b.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>American Epilepsy Society</b>
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</div><div>
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<a href="https://www.aesnet.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aesnet.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Canadian Epilepsy Alliance</b>
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</div><div>Canada</div><div><b>Phone:</b> 1-866-EPILEPSY (1-866-374-5377)</div><div>
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<a href="https://www.canadianepilepsyalliance.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">canadianepilepsyalliance.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Epilepsy Canada</b>
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</div><div>Canada</div><div><b>Phone:</b> 877-734-0873</div><div><b>Email:</b> epilepsy@epilepsy.ca</div><div>
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<a href="http://www.epilepsy.ca/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.ca</a>
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</div></li><li class="half_rhythm"><div>
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<b>Epilepsy Foundation</b>
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</div><div><b>Phone:</b> 800-332-1000; 866-748-8008</div><div>
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<a href="https://www.epilepsy.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Institute of Neurological Disorders and Stroke (NINDS)</b>
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</div><div><b>Phone:</b> 800-352-9424</div><div>
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<a href="https://www.ninds.nih.gov/Disorders/All-Disorders/Epilepsy-Information-Page" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy and Seizures</a>
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</div></li><li class="half_rhythm"><div>
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<b>GRIN Registry</b>
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</div><div>
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<a href="https://grin-portal.broadinstitute.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">grin-portal.broadinstitute.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Simons Searchlight Registry</b>
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</div><div>
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<i>Simons Searchlight aims to further the understanding of rare genetic neurodevelopmental disorders.</i>
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</div><div><b>Phone:</b> 855-329-5638</div><div><b>Fax:</b> 570-214-7327</div><div><b>Email:</b> coordinator@simonssearchlight.org</div><div>
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<a href="https://www.simonssearchlight.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">simonssearchlight.org</a>
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</div></li></ul>
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</div><div id="grin2b.Molecular_Genetics"><h2 id="_grin2b_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bmolgenTA"><a href="/books/NBK501979/table/grin2b.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobgrin2bmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.molgen.TA"><a href="/books/NBK501979/table/grin2b.molgen.TA/?report=objectonly" target="object" rid-ob="figobgrin2bmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">GRIN2B-Related Neurodevelopmental Disorder: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figgrin2bmolgenTB"><a href="/books/NBK501979/table/grin2b.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobgrin2bmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="grin2b.molgen.TB"><a href="/books/NBK501979/table/grin2b.molgen.TB/?report=objectonly" target="object" rid-ob="figobgrin2bmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for GRIN2B-Related Neurodevelopmental Disorder (View All in OMIM) </p></div></div><div id="grin2b.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels expressed throughout the brain mediating excitatory neurotransmission. Signaling via NMDAR plays an important role in brain development, learning, memory, and other higher cognitive functions. NMDAR are diheterotetramers or triheterotetramers composed of two glycine-binding GluN1subunits (encoded by <i>GRIN1</i>) and two glutamate-binding GluN2 subunits (<i>GRIN2A</i> through <i>GRIN2D</i>) [<a class="bibr" href="#grin2b.REF.traynelis.2010.405" rid="grin2b.REF.traynelis.2010.405">Traynelis et al 2010</a>]. Simultaneous binding of both agonists activates the NMDAR, which opens a cation-selective pore leading to an influx of Ca<sup>2+</sup> and depolarization.</p><p>Compared with the ubiquitously expressed GluN1 subunits, the GluN2 subunits show specific spatiotemporal expression profiles throughout the central nervous system [<a class="bibr" href="#grin2b.REF.paoletti.2013.383" rid="grin2b.REF.paoletti.2013.383">Paoletti et al 2013</a>]. The GluN2B and GluN2D subunits are expressed prenatally, whereas expression of the GluN2A and GluN2C subunits significantly increases shortly after birth. Over time, postnatal expression of GluN2B is progressively restricted to the forebrain in rat and mouse models.</p><p><b>Gene structure.</b>
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<i>GRIN2B</i> spans about 400 kb of genomic DNA and comprises 13 exons (transcript <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000834.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000834.4</a>). For a detailed summary of gene and protein information, see <a href="/books/NBK501979/?report=reader#grin2b.molgen.TA">Table A</a>, <b>Gene</b>.</p><p><b>Pathogenic variants.</b> Missense, nonsense, frameshift, and splicing pathogenic variants have been reported (see <a href="/books/NBK501979/?report=reader#grin2b.molgen.TA">Table A</a>, <b>Locus-Specific</b>
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<b>Databases</b>) [<a class="bibr" href="#grin2b.REF.endele.2010.1021" rid="grin2b.REF.endele.2010.1021">Endele et al 2010</a>, <a class="bibr" href="#grin2b.REF.tarabeux.2011.e55" rid="grin2b.REF.tarabeux.2011.e55">Tarabeux et al 2011</a>, <a class="bibr" href="#grin2b.REF.de_ligt.2012.1921" rid="grin2b.REF.de_ligt.2012.1921">de Ligt et al 2012</a>, <a class="bibr" href="#grin2b.REF.oroak.2012.1619" rid="grin2b.REF.oroak.2012.1619">O'Roak et al 2012</a>, <a class="bibr" href="#grin2b.REF.allen.2013.217" rid="grin2b.REF.allen.2013.217">Allen et al 2013</a>, <a class="bibr" href="#grin2b.REF.dimassi.2013.2564" rid="grin2b.REF.dimassi.2013.2564">Dimassi et al 2013</a>, <a class="bibr" href="#grin2b.REF.freunscht.2013.20" rid="grin2b.REF.freunscht.2013.20">Freunscht et al 2013</a>, <a class="bibr" href="#grin2b.REF.adams.2014.161" rid="grin2b.REF.adams.2014.161">Adams et al 2014</a>, <a class="bibr" href="#grin2b.REF.hamdan.2014.e1004772" rid="grin2b.REF.hamdan.2014.e1004772">Hamdan et al 2014</a>, <a class="bibr" href="#grin2b.REF.kenny.2014.872" rid="grin2b.REF.kenny.2014.872">Kenny et al 2014</a>, <a class="bibr" href="#grin2b.REF.lemke.2014.147" rid="grin2b.REF.lemke.2014.147">Lemke et al 2014</a>, <a class="bibr" href="#grin2b.REF.oroak.2014.5595" rid="grin2b.REF.oroak.2014.5595">O'Roak et al 2014</a>, <a class="bibr" href="#grin2b.REF.deciphering_developmental_disorders_study_group.2015.223" rid="grin2b.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group 2015</a>, <a class="bibr" href="#grin2b.REF.grozeva.2015.1197" rid="grin2b.REF.grozeva.2015.1197">Grozeva et al 2015</a>, <a class="bibr" href="#grin2b.REF.yavarna.2015.967" rid="grin2b.REF.yavarna.2015.967">Yavarna et al 2015</a>, <a class="bibr" href="#grin2b.REF.zhang.2015.e0141782" rid="grin2b.REF.zhang.2015.e0141782">Zhang et al 2015</a>, <a class="bibr" href="#grin2b.REF.zhu.2015.774" rid="grin2b.REF.zhu.2015.774">Zhu et al 2015</a>, <a class="bibr" href="#grin2b.REF.bosch.2016.660" rid="grin2b.REF.bosch.2016.660">Bosch et al 2016</a>, <a class="bibr" href="#grin2b.REF.retterer.2016.696" rid="grin2b.REF.retterer.2016.696">Retterer et al 2016</a>, <a class="bibr" href="#grin2b.REF.smigiel.2016.3265" rid="grin2b.REF.smigiel.2016.3265">Smigiel et al 2016</a>, <a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>].</p><p>Of note, discussion of the phenotypes associated with large rearrangements at 12p13.1 that involve <i>GRIN2B</i> – and often contiguous genes – have not been included in this <i>GeneReview</i> because the observed clinical findings cannot be attributed with assurance solely to <i>GRIN2B.</i> Nonetheless, these deletions [<a class="bibr" href="#grin2b.REF.dimassi.2013.2564" rid="grin2b.REF.dimassi.2013.2564">Dimassi et al 2013</a>], translocations, apparently balanced chromosome rearrangements, and inversions [<a class="bibr" href="#grin2b.REF.endele.2010.1021" rid="grin2b.REF.endele.2010.1021">Endele et al 2010</a>, <a class="bibr" href="#grin2b.REF.talkowski.2012.525" rid="grin2b.REF.talkowski.2012.525">Talkowski et al 2012</a>] are mentioned here for completeness. Three interstitial deletions in 12p13.1 involving parts of <i>GRIN2B</i> are non-recurrent and range in size from 0.58 Mb to 4.1 Mb [<a class="bibr" href="#grin2b.REF.dimassi.2013.2564" rid="grin2b.REF.dimassi.2013.2564">Dimassi et al 2013</a>]. All deletions involve neighboring genes: the shortest one resulted in a deletion of the first exon of <i>GRIN2B</i> and the neighboring gene <i>ATF7IP</i>, which corresponds to the minimal region of overlap; the other two deletions comprise 29 and 21 neighboring genes.</p><p><b>Normal gene product.</b> The protein consists of 1,484 amino acids and contains an amino-terminal domain, two ligand-binding domains (S1 and S2), four transmembrane domains (M1-M4), and a C-terminal domain.</p><p><b>Abnormal gene product.</b> Pathogenic missense variants cluster within or in very close proximity to the ligand-binding domains S1 and S2, as well as the transmembrane domains M1-M4 [<a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al 2017</a>].</p></div></div><div id="grin2b.Chapter_Notes"><h2 id="_grin2b_Chapter_Notes_">Chapter Notes</h2><div id="grin2b.Author_Notes"><h3>Author Notes</h3><p>Konrad Platzer, MD<br />Institute of Human Genetics<br />University of Leipzig Hospitals and Clinics<br />Philipp-Rosenthal-Str. 55<br />04103 Leipzig, Germany</p><p>Johannes R Lemke, MD<br />Institute of Human Genetics<br />University of Leipzig Hospitals and Clinics<br />Philipp-Rosenthal-Str. 55<br />04103 Leipzig, Germany</p><p>
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<a href="https://www.uniklinikum-leipzig.de/einrichtungen/humangenetik" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Institute of Human Genetics</a>
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</p><p>
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<a href="https://www.grin-database.de/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GRIN Database</a>
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</p></div><div id="grin2b.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>25 March 2021 (aa) Revision: incorporated parental mosaicism data from <a class="bibr" href="#grin2b.REF.myers.2018.1646" rid="grin2b.REF.myers.2018.1646">Myers et al [2018]</a></div></li><li class="half_rhythm"><div>31 May 2018 (bp) Review posted live</div></li><li class="half_rhythm"><div>30 October 2017 (jrl) Original submission</div></li></ul></div></div><div id="grin2b.References"><h2 id="_grin2b_References_">References</h2><div id="grin2b.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="grin2b.REF.adams.2014.161">Adams
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DR, Yuan
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H, Holyoak
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T, Arajs
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KH, Hakimi
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P, Markello
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TC, Wolfe
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LA, Vilboux
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T, Burton
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BK, Fajardo
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KF, Grahame
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G, Holloman
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C, Sincan
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M, Smith
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AC, Wells
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GA, Huang
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Y, Vega
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H, Snyder
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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Platzer K, Lemke JR. GRIN2B-Related Neurodevelopmental Disorder. 2018 May 31 [Updated 2021 Mar 25]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/grin2a-dis/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/grin2d-dee/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobgrin2bTmoleculargenetictestingused"><div id="grin2b.T.molecular_genetic_testing_used" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>GRIN2B</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.T.molecular_genetic_testing_used/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.T.molecular_genetic_testing_used_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GRIN2B</i>
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</td><td headers="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">82/86 <sup>4</sup></td></tr><tr><td headers="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup> or chromosomal microarray (CMA) <sup>6</sup></td><td headers="hd_h_grin2b.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4/86 <sup>4</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="grin2b.TF.1.1"><p class="no_margin">See <a href="/books/NBK501979/?report=reader#grin2b.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="grin2b.TF.1.2"><p class="no_margin">See <a href="#grin2b.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="grin2b.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="grin2b.TF.1.4"><p class="no_margin">For references, see <a href="#grin2b.Molecular_Pathogenesis">Molecular Pathogenesis</a>, <b>Pathogenic variants</b>. Note: Three additional individuals with contiguous gene deletions (not included in these calculations) have been reported: two with chromosome translocations and one with a chromosome inversion disrupting <i>GRIN2B</i> [<a class="bibr" href="#grin2b.REF.endele.2010.1021" rid="grin2b.REF.endele.2010.1021">Endele et al 2010</a>, <a class="bibr" href="#grin2b.REF.talkowski.2012.525" rid="grin2b.REF.talkowski.2012.525">Talkowski et al 2012</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="grin2b.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="grin2b.TF.1.6"><p class="no_margin">Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>GRIN2B</i>) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 12p13.1 region (which includes <i>GRIN2B</i>). CMA designs in current clinical use target the 12p13.1 region.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgrin2bTgenestoconsiderinthediffer"><div id="grin2b.T.genes_to_consider_in_the_differ" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Genes to Consider in the Differential Diagnosis of <i>GRIN2B</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.T.genes_to_consider_in_the_differ/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.T.genes_to_consider_in_the_differ_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotype</th><th id="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genes <sup>1</sup></th><th id="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>GeneReview</i>/OMIM/Reference</th></tr></thead><tbody><tr><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intellectual disability</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>180</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Autosomal dominant: OMIM <a href="https://omim.org/phenotypicSeries/PS156200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS156200</a><br />Autosomal recessive: OMIM <a href="https://omim.org/phenotypicSeries/PS249500" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS249500</a><br />Nonsyndromic, X-linked: OMIM <a href="https://omim.org/phenotypicSeries/PS309530" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS309530</a><br />Syndromic, X-linked: OMIM <a href="https://omim.org/phenotypicSeries/PS309510" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS309510</a></td></tr><tr><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-onset epileptic encephalopathy</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>50</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/phenotypicSeries/PS308350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS308350</a></td></tr><tr><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Polymicrogyria</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~50</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a class="bibr" href="#grin2b.REF.stutterd.2020.fcaa221" rid="grin2b.REF.stutterd.2020.fcaa221">Stutterd et al [2020]</a>, <a class="bibr" href="#grin2b.REF.james.2022.616" rid="grin2b.REF.james.2022.616">James et al [2022]</a></td></tr><tr><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tubulinopathies</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TUBA1A</i>
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<br />
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<i>TUBA8</i>
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<br />
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<i>TUBB</i>
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<br />
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<i>TUBG1</i>
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<br />
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<i>TUBB2A</i>
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<br />
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<i>TUBB2B</i>
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<br />
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<i>TUBB3</i>
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</td><td headers="hd_h_grin2b.T.genes_to_consider_in_the_differ_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/tubulin-ov/?report=reader">Tubulinopathies Overview</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="grin2b.TF.2.1"><p class="no_margin">See linked <i>GeneReview</i> or OMIM phenotypic series entry for further information.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgrin2bTrecommendedevaluationsfollowi"><div id="grin2b.T.recommended_evaluations_followi" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.T.recommended_evaluations_followi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.T.recommended_evaluations_followi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ocular</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for cortical visual impairment.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal/</b>
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<br />
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<b>Feeding</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding, nutrition status, weight gain</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Determine if tube feeding is required.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical eval for tone abnormalities</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for muscular hypotonia &/or spasticity.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl clinical eval for movement disorders, EEG, brain MRI</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
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<br />
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<b>Behavioral</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For persons age >12 mos: screen for concerns incl sleep disturbances, ADHD, anxiety, &/or findings suggestive of ASD.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Miscellaneous/</b>
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<br />
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<b>Other</b>
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</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl motor, speech & language, general cognitive, vocational skills</td></tr><tr><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_grin2b.T.recommended_evaluations_followi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgrin2bTtreatmentofmanifestationsin"><div id="grin2b.T.treatment_of_manifestations_in" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.T.treatment_of_manifestations_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.T.treatment_of_manifestations_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Abnormal vision &/or strabismus</b>
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</td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by experienced ophthalmologist</td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Seizures</b>
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</td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment w/ASM by experienced neurologist <sup>1</sup></td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</td></tr><tr><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypotonia, spasticity, & movement disorder</b>
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</td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by experienced neurologist</td><td headers="hd_h_grin2b.T.treatment_of_manifestations_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="grin2b.TF.4.1"><p class="no_margin">Education of parents regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgrin2bTrecommendedsurveillanceforin"><div id="grin2b.T.recommended_surveillance_for_in" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>GRIN2B</i>-Related Neurodevelopmental Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.T.recommended_surveillance_for_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.T.recommended_surveillance_for_in_lrgtbl__"><table><thead><tr><th id="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ocular</b>
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_3" rowspan="6" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal</b>
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feeding, nutrition status, weight gain</td></tr><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor gross & fine motor development in those w/tone abnormalities.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor treatment effectiveness in those w/seizures, movement disorders, &/or spasticity.</td></tr><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric</b>
|
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavioral assessment for anxiety, attention, & aggressive or self-injurious behavior</td></tr><tr><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Miscellaneous/</b>
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<br />
|
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<b>Other</b>
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</td><td headers="hd_h_grin2b.T.recommended_surveillance_for_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobgrin2bmolgenTA"><div id="grin2b.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>GRIN2B-Related Neurodevelopmental Disorder: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_grin2b.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_grin2b.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_grin2b.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_grin2b.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_grin2b.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_grin2b.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_grin2b.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/2904" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>GRIN2B</i>
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</a>
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</td><td headers="hd_b_grin2b.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2904" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12p13<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_b_grin2b.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/Q13224" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Glutamate receptor ionotropic, NMDA 2B</a>
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</td><td headers="hd_b_grin2b.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://databases.lovd.nl/shared/genes/GRIN2B" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GRIN2B @ LOVD</a>
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<br />
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<a href="https://www.grin-database.de" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GRIN Database - GRIN2B</a>
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</td><td headers="hd_b_grin2b.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GRIN2B" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GRIN2B</a>
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</td><td headers="hd_b_grin2b.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GRIN2B[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GRIN2B</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="grin2b.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobgrin2bmolgenTB"><div id="grin2b.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for GRIN2B-Related Neurodevelopmental Disorder (<a href="/omim/138252,613970,616139" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK501979/table/grin2b.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__grin2b.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/138252" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">138252</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GLUTAMATE RECEPTOR, IONOTROPIC, N-METHYL-D-ASPARTATE, SUBUNIT 2B; GRIN2B</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/613970" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613970</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 6, WITH OR WITHOUT SEIZURES; MRD6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/616139" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">616139</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 27; DEE27</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobgrin2bF1"><div id="grin2b.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK501979/bin/grin2b-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>MRI of individuals with malformation of cortical development</p><p>A-D: patient 1; E-H: patient 2; I-L: patient 3; M-P: patient 4; Q-T: patient 5; U-X: patient 6; AA-DD: normal control</p><p>Column 1. T<sub>1</sub>-weighted midsagittal images. All are normal except for mildly low forehead in individuals A, I, U; however, several are slightly off the midline.</p><p>Column 2. T<sub>2</sub>-weighted axial images through the basal ganglia showing relatively large and mildly dysplastic basal ganglia (asterisks in B, F, J, N, R, and V) compared with normal.</p><p>Column 3. T<sub>2</sub>-weighted axial images through the higher lateral ventricles showing a diffuse irregular gyral pattern. White arrows indicate small gyri and limited intracortical microgyri in the left hemisphere, an appearance intermediate between typical polymicrogyria and the cortical appearance of tubulinopathies.</p><p>Column 4. T<sub>2</sub>-weighted coronal images through the hippocampus. Black arrows indicate hippocampal dysplasia with thick leaves and open hilus, ranging from severe (D, H, X) to moderate (L, P).</p><p>Reproduced with permission from <a class="bibr" href="#grin2b.REF.platzer.2017.460" rid="grin2b.REF.platzer.2017.460">Platzer et al [2017]</a></p></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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