DNA icon

Focal Epilepsy with Speech Disorder via the GRIN2A Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
GRIN2A 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4167GRIN2A81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Focal epilepsy with speech disorder (FESD) is a neurocognitive disease with an age of onset ranging from infancy to nine years. Major clinical features include speech and language disability (100%), childhood onset focal seizures (90%), and mild to moderate intellectual disability (38-67%). Minor features of GRIN2A-related disease (<50% of cases) include autism spectrum disorder and severe intellectual disability (Carvill et al. 2013. PubMed ID: 23933818; Lesca et al. 2013. PubMed ID: 23933820; Lemke et al. 2013. PubMed ID: 23933819). Focal epilepsy with speech disorder is an ultra-rare condition with less than 40 disease-associated variants reported to date.

FESD encompasses a spectrum of epilepsy phenotypes of varying severities including: Landau-Kleffner syndrome (LKS), continuous spike and waves during slow-wave sleep syndrome (CSWSS) and benign epilepsy of childhood with centrotemporal spikes (BECTS)/Rolandic epilepsy. A characteristic feature of FESD-related disorders is centrotemporal spikes or electrical status epilepticus during sleep (ESES) as revealed by EEG recordings (Reutlinger et al. 2010. PubMed ID: 20384727). The presence of ESES during sleep is believed to contribute to cognitive and language impairment. LKS and CSWS are both considered epileptic encephalopathies and have overlapping clinical features including seizures of various types, epileptiform activity during sleep and developmental regression. LKS patients present with seizures at 2-8 years of age and then undergo language regression in the form of aphasia (Caraballo et al. 2014. PubMed ID: 24315829).

LKS patients may have delayed speech development and subsequently lose receptive and expressive language. Verbal agnosia, where individuals fail to understand spoken language, is also commonly observed. Seizures and ESES activity remit around the onset of puberty in LKS patients (Sánchez Fernández et al. 2012. PubMed ID: 23127259).

CSWS patients present with seizures at 2-4 years of age, and global developmental regression is seen around 5-6 years. Around 10 years of age patients become seizure free and ESES EEG pattern resolves, but neurocognitive impairments persist (Sánchez Fernández et al. 2013. PubMed ID: 23991336). Unlike LKS patients, CSWS patients experience regression in motor skills, language and overall cognitive function.

BECTS patients present with seizures during sleep between 7 and 10 years of age. Seizures manifest as a choking sensation, asymmetric clonic spasms of the mouth, drooling and grunting (Sánchez Fernández et al. 2012. PubMed ID: 23127259). Seizures last for 1-2 minutes and 50% of the time consciousness is maintained throughout the episode. Seizures remit during adolescence. BECTS is not associated with developmental regression.

Reaching a genetic diagnosis in individuals with neurocognitive disorders has been shown to provide emotional support to families including “acceptance” and “hope” and may have family planning implications (Reiff et al. 2017. PubMed ID: 28229350). Furthermore, identifying the genetic cause of epilepsy disorders can aid in guiding precision medicine (Truty et al. 2019. PubMed ID: 1440721). Early indicators suggest that individuals with FESD may benefit from memantine (Pierson et al. 2014. PubMed ID: 24839611). 


FESD is inherited in an autosomal dominant manner and is caused by variations in the GRIN2A gene. The penetrance of FESD is incomplete, suggesting that other genetic or environmental factors may act as modifiers of the phenotype. De novo large deletions of 16p13 encompassing GRIN2A have been reported in individuals with intellectual disability, focal seizures and autism spectrum disorders (Reutlinger et al. 2010. PubMed ID: 20384727; Lesca et al. 2012. PubMed ID: 22738016). Nearly all molecular variant types have been associated with GRIN2A-related disease. Pathogenic missense variants are the most frequently reported. They are enriched in the agonist binding domains (S1 and S2) and pore forming transmembrane domains (M1-4). These regions are depleted of natural missense variation in the general population (Karczewski et al. 2020. PubMed ID: 32461654; Swanger et al. 2016. PubMed ID: 27839871). Pathogenic missense variants have been shown to affect several biophysical properties including, agonist binding, channel gating, and receptor biogenesis. What is surprising is that variants predicted to result in loss- or gain-of receptor function appear to cause similar neurological phenotypes (Swanger et al. 2016. PubMed ID: 27839871). Predicted null variants (nonsense, frameshifts, and large deletions) are believed to cause disease by haploinsufficiency (Endele et al. 2010. PubMed ID: 20890276), and GRIN2A is intolerant to chain-terminating variants (Genome Aggregation Database; Karczewski et al. 2020. PubMed ID: 32461654).

GRIN2A encodes the alpha-2B subunit of N-methyl d-aspartate (NMDA) receptors. These ligand-gated ion channels bind glutamate and glycine and serve as important detectors of activity for synaptic plasticity, learning, and memory. NMDA receptors are heterotetrameric, composed of one alpha-1 subunit and one or more alpha-2 A, B, C, or D subunit. This composition is dependent on developmental timing, with GRIN2A expression arising later in development (Endele et al. 2010. PubMed ID: 20890276). GRIN2A knockout mice exhibit impaired spatial learning and reduced long term potentiation in the hippocampus (Sakimura et al. 1995. PubMed ID: 7816096). GRIN2A has been cited as a nonessential gene for growth of human tissue culture cells (Online Gene Essentiality, ogee.medgenius.info).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of this test may be as high as ~7-12% among patients with FESD (Carvill et al. 2013. PubMed ID: 23933818; Lesca et al. 2013. PubMed ID: 23933820; Lemke et al. 2013. PubMed ID: 23933819). Including a broader phenotype, another study identified pathogenic GRIN2A variants in ~1.5% (2/127) of individuals with a history of idiopathic epilepsy and varying degrees of intellectual disability (Endele et al. 2010. PubMed ID: 20890276). Since the majority of pathogenic variants in GRIN2A involve single base pair substitutions, the analytical sensitivity of this test is predicted to be very high (>99%).

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the GRIN2A gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Indications for Test

GRIN2A testing may be considered in patients with symptoms of FESD or related disorders such as idiopathic focal epilepsy, electrical status epilepticus during sleep and acquired aphasia. Targeted testing is indicated for family members of patients who have a known pathogenic variant in GRIN2A.


Official Gene Symbol OMIM ID
GRIN2A 138253
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Early Infantile Epileptic Encephalopathy Panel


  • Caraballo et al. 2014. PubMed ID: 24315829
  • Carvill et al. 2013. PubMed ID: 23933818
  • Endele et al. 2010. PubMed ID: 20890276
  • Genome Aggregation Database (gnomAD).
  • Karczewski et al. 2020. PubMed ID: 32461654
  • Lemke et al. 2013. PubMed ID: 23933819
  • Lesca et al. 2012. PubMed ID: 22738016
  • Lesca et al. 2013. PubMed ID: 23933820
  • Online Gene Essentiality (OGEE).
  • Pierson et al. 2014. PubMed ID: 24839611
  • Reiff et al. 2017. PubMed ID: 28229350
  • Reutlinger et al. 2010. PubMed ID: 20384727
  • Sakimura et al. 1995. PubMed ID: 7816096
  • Sánchez Fernández et al. 2012. PubMed ID: 23127259
  • Sánchez Fernández et al. 2013. PubMed ID: 23991336
  • Swanger et al. 2016. PubMed ID: 27839871
  • Truty et al. 2019. PubMed ID: 31440721


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard