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Journal of Pediatric Neurology 2023; 21(03): 212-223
DOI: 10.1055/s-0041-1727146
Review Article

GRIN2A and GRIN2B and Their Related Phenotypes

Authors

  • Annamaria Sapuppo‡   *

    1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

  • Laura Portale‡   *

    1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

  • Carmela R. Massimino

    1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

  • Santiago Presti

    1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

  • Lucia Tardino

    2   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

  • Simona Marino

    2   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

  • Agata Polizzi

    3   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy

  • Raffaele Falsaperla

    2   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
    4   Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

  • Andrea D. Praticò 

    5   Unit of Rare Diseases of the Nervous Systemin Childhood, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
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Abstract

Glutamate is the most relevant excitatory neurotransmitter of the central nervous system; it binds with several receptors, including N-methyl-D-aspartate receptors (NMDARs), a subtype of ionotropic glutamate receptor that displays voltage-dependent block by Mg2+ and a high permeability to Ca2+. GRIN2A and GRIN2B genes encode the GluN2A and GluN2B subunits of the NMDARs, which play important roles in synaptogenesis, synaptic transmission, and synaptic plasticity, as well as contributing to neuronal loss and dysfunction in several neurological disorders. Recently, individuals with a range of childhood-onset drug-resistant epilepsies, such as Landau–Kleffner or Lennox–Gastaut syndrome, intellectual disability (ID), and other neurodevelopmental abnormalities have been found to carry mutations in GRIN2A and GRIN2B, with high variable expressivity in phenotype. The first one is found mainly in epilepsy-aphasia syndromes, while the second one mainly in autism, schizophrenia, and ID, such as autism spectrum disorders. Brain magnetic resonance imaging alterations are found in some patients, even if without a clear clinical correlation. At the same time, increasing data on genotype–phenotype correlation have been found, but this is still not fully demonstrated. There are no specific therapies for the treatment of correlated NMDARs epilepsy, although some evidence with memantine, an antagonist of glutamate receptor, is reported in the literature in selected cases with mutation determining a gain of function.

Keywords

GRIN2A - GRIN2B - glutamate - epilepsy-aphasia spectrum - Landau–Kleffner syndrome - Lennox–Gastaut syndrome

* These authors have equally contributed to the present article.




Publication History

Received: 20 February 2021

Accepted: 21 February 2021

Article published online:
21 May 2021

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