Two patients with a GRIN2A mutation and childhood-onset epilepsy< /strong> < /h2>

Original research article by S.P. DeVries and A.D. Patel et al. < /em> (2013) < /p>

Read the abstract here< /a> . < /p>

Neurotransmitters are chemicals that aid in signaling between nerve cells in the brain. Genetic changes in GRIN2A can have an impact on neurotransmitter function and have been linked to childhood-onset epilepsy of varying degrees of severity, as well as to autism and other neurological disorders. The authors of this paper describe the clinical features of two people with changes in GRIN2A. < /p>

Patient #1 was a 3-year-old boy with global developmental delay. It was reported that he experienced his first seizure at the age of two. An EEG revealed abnormalities, and microarray testing showed he had a deletion of most of the¬ †GRIN2A ¬ < /em>gene. He had a wide gait (walking pattern) and was reported as being seizure-free for six months with the help of medication. After six months, he developed seizures again, and was unsteady on his feet. After adjustments in medication dosages and physical therapy, he once again became seizure-free and experienced an improvement in walking. Patient #1‚ Ä ôs mother also had a history of childhood-onset seizures and was found to have the same gene change as her son. < /p>

Patient #2 was a 9-year-old boy who experienced multiple types of seizures beginning at age 4. He experienced over 100 seizures a day, and numerous medications and treatments failed to decrease the frequency of his seizures. Whole-exome sequencing showed he had a change in GRIN2A. His development was reported to have been normal initially but to have declined at age 4, after his seizures began. Patient #2‚ Ä ôs father was found to have the same change. He did not report a history of seizures but did have a history of major depressive disorder. See the table below for a comparison of the two people‚ Ä ôs characteristics. < /p>

These case studies, as well as other literature, show that people with a change in the¬ †GRIN2A¬ †gene can have a wide range of issues, including seizures. This research suggests that future genetic tests for childhood-onset epilepsy should screen for changes in¬ †GRIN2A. < /p>

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white; background-color: #f36046; padding: 5px; border: 1px solid #d9d9d9; text-align: center;" colspan="3"> Comparison of genetic and clinical findings (Table 1 from DeVries et al. paper) < /strong> < /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> < /td> white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Patient 1< /strong> < /td> white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Patient 2< /strong> < /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Genetic Findings< /strong> < /td> 5px; border: 1px solid #d9d9d9;">16p13.2 microdeletion involving the majority of the GRIN2A gene (292.09 kb) , exons 4-14< /td> 5px; border: 1px solid #d9d9d9;">V506A variant in the GRIN2A gene< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Seizure type< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Focal seizures< /td> 5px; border: 1px solid #d9d9d9;">Focal seizures, Myoclonus, Atypical absence< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Description< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Left facial twitching, drooling, teeth grinding, arm/leg jerking followed by transient paralysis and postictal state< /td> 5px; border: 1px solid #d9d9d9;">Arrest in activity, right hand twitching, upward eye deviation, jerking forward. He can say a few words, but cannot carry on a conversation. < /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Duration< /strong> < /td> 5px; border: 1px solid #d9d9d9;">1-3 min. Longest event 20 min< /td> 5px; border: 1px solid #d9d9d9;">30 seconds to 15 min. Longest event greater than 1 hour< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Frequency< /strong> < /td> 5px; border: 1px solid #d9d9d9;">One per 1-2 months< /td> 5px; border: 1px solid #d9d9d9;">More than 100 per day< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Current medications and treatments< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Levetiracetam< /td> 5px; border: 1px solid #d9d9d9;">Clobazam, felbamate, vagus nerve stimulator< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Failed medications and treatments< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Oxcarbazepine< /td> 5px; border: 1px solid #d9d9d9;">Levetiracetam, zonisamide, lamotrigine, lacosamide, clonazepam, ethosuximide, brivaracetam, topiramate, oxcarbazepine, valproic acid, vitamin B6, ketogenic diet< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Development< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Delayed cognition, motor, and speech. Receives PT/OT and attends a special needs preschool< /td> 5px; border: 1px solid #d9d9d9;">Normal when seizure free; cognitive and language delay when refractory< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Electroencephalograph findings< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Frequent, multifocal spikes, polyspike-wave discharges, left greater than right posterior quadrant< /td> 5px; border: 1px solid #d9d9d9;">Generalized bisynchronous 2-2.5 Hz slow spike waves and left frontotemporal discharges and electrographic seizure from the left centrotemporal region. < /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Imaging< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Noncontrast MRI normal< /td> 5px; border: 1px solid #d9d9d9;">Noncontrast MRI normal
/ > PET: diffuse cortical hypometabolism, minimal
/ > asymmetry within the left lateral
/ > temporoparietal region
/ > SPECT: increased uptake near the vertex, at the
/ > frontoparietal junction, more extensive on the
/ > left side, more intense on the right< /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Parental testing< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Mother with identical mutation. < /td> 5px; border: 1px solid #d9d9d9;">Father with identical mutation. < /td> < /tr>
white; background-color: #f36046; text-align: center; padding: 5px; border: 1px solid #d9d9d9;"> Family history< /strong> < /td> 5px; border: 1px solid #d9d9d9;">Mother had childhood-onset epilepsy and is currently seizure-free off of AEDs. Maternal uncle with epilepsy. < /td> 5px; border: 1px solid #d9d9d9;">Father: major depressive disorder< /td> < /tr>
5px; border: 1px solid #d9d9d9;" colspan="3">Abbreviations:
/ > AED = Antiepilepsy drug
/ > MRI = Magnetic resonance imaging
/ > NF-1 = Neurofibromatosis type 1
/ > OT = Occupational therapy
/ > PET = Positron emission tomography
/ > PT = Physical therapy
/ > SPECT = Single photon emission computed tomography< /td> < /tr> < /tbody> < /table>

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