Dados do Trabalho

Título

CHILDHOOD EPILEPSY DUE TO ALTERATION IN THE GRIN2B GENE: A CASE REPORT.

Apresentação do caso

Case Presentation: A male patient at five months of age was taken to a pediatric neurology clinic with a presentation of delayed psychomotor development and mild muscle spasms accompanied by binocular supraversion for two months, occurring frequently at five times per day with an average duration of one minute per episode, triggered when the patient became irritated or cried. Additionally, the child presented with significant axial hypotonia, low nasal bridge, epicanthic folds, low-set ears, protuberant heels, and a gaze that did not follow or fixate on eye contact. Neurological examination demonstrated head control acquisition, tetraparesis with hypotonia, grade II symmetric reflexes, indifferent bilateral plantar cutaneous reflex, and intact cranial nerves with isocoric, photoreactive pupils and preserved extraocular motility, including occasional divergent strabismus. A cranial magnetic resonance imaging revealed no structural brain abnormalities or abnormal myelination. An electroencephalogram detected frequent interictal epileptiform activity in the left centro-parieto-temporal region with rare multifocal abnormalities, diffuse slowing of low amplitude, and asymmetry of the baseline activity. Comparative genomic hybridization array was used to identify possible chromosomal alterations causing infantile epileptic encephalopathy, showing a paternally inherited 170kb duplication in band 3p25.2 on the short arm of chromosome 3 and another in region 10q26.3, which did not fully explain the patient's phenotype. Whole-exome sequencing detected a GRIN2B gene alteration with the variant Chr 12:13,720,098 promoting the substitution of glycine for valine at codon 820 (p.Gly820Val), which was not inherited from the parents, indicating a mutational event.

Discussão

Discussion: The GRIN2B gene, located on the short arm of chromosome 12 at 12p13.1, encodes the GluN2B subunit of the N-methyl-D-aspartate receptor, generating neural excitations. Whole-exome sequencing allowed the detection of an extensive number of variants in the GRIN2B gene, which have direct implications in various neurodevelopmental disorders such as intellectual disability, autism spectrum disorder, visual impairment, and infantile epileptic encephalopathy.

Comentários finais

Final Comments: The importance of investigating genetic mutations using available tests in the field must be underscored as a possible cause of epileptic syndromes, aiming to provide therapeutic support to patients and improve their quality of life.

Referências (se houver)

1.Cendes IL, Ribeiro PA. Aspectos genéticos das epilepsias: uma visão atual. Rev Med Clin Condes 2013;24:903-8. https://doi.org/10.1016/S0716-8640(13)70243-8
2.Benke TA, Kristen Park, Ilona Krey, Chad R. Camp, Rui Song, Amy J. Ramsey, et al. Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs. Neuropharmacology 2021;199:108805. https://doi.org/10.1016/j.neuropharm.2021.108805
3.Endele S, Rosenberger G, Geider K, Popp B, Tamer C, Stefanova I, et al. Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat Genet 2010;42:1021-6. https://doi.org/10.1038/ng.677
4.Akazawa C, Shigemoto R, Bessho Y, Nakanishi S, Mizuno N. Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J Comp Neurol 1994;347:150-60. https://doi.org/10.1002/cne.903470112
5.Pouyan M Donya, Faraji Niloofar, Rezaei Sajjad, Keshavarz Parvaneh. Single-locus and Haplotype Associations of GRIN2B Gene with Autism Spectrum Disorders and the Demographic and Clinical Characteristics of Patients in Guilan, Iran. Journal of Autism and Developmental Disorders (2022). https://doi.org/10.1007/s10803-022-05818-2
6.Lemke JR, Hendrickx R, Geider K, Laube B, Schwake M, Harvey RJ, et al. GRIN2B mutations in west syndrome and intellectual disability with focal epilepsy. Ann Neurol 2014;75:147-54. https://doi.org/10.1002/ana.24073
7.Martins R, Moldovan O, Sousa AB, Levy A, Quintas S. Epileptic Encephalopathies of Childhood: The New Paradigm of Genetic Diagnosis. Acta Med Port 2020;33:415-24. https://doi.org/10.20344/amp.12550
8.Hamdan FF, Srour M, Capo-Chichi JM, Daoud H, Nassif C, Patry L, et al. De novo mutations in moderate or severe intellectual disability. PLoS Genet 2014;10:e1004772. https://doi.org/10.1371/journal.pgen.1004772
9.Talkowski ME, Rosenfeld JA, Blumenthal I, Pillalamarri V, Chiang C, Heilbut A, et al. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 2012;149:525-37. https://doi.org/10.1016/j.cell.2012.03.028
10.Myers SJ, Yuan H, Kang JQ, Tan Kuan FC, Traynelis SF. Distinct roles of GRIN2A and GRIN2B variants in neurological conditions. F1000 Research 2019. https://doi.org/10.12688%2Ff1000research.18949.1

Palavras Chave

Epileptic Seizure; Encephalopathy; Databases Genetic; Mutation; Neurodevelopmental Disorders.

Fonte de Fomento (se houver)

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Área

Neurogenética