Heterozygous SLC1A2 mutation in a child with early infantile seizures and global developmental delay
DOI:
https://doi.org/10.18203/2349-3291.ijcp20220460Keywords:
Infantile refractory seizures, Global developmental delay, Genetic epilepsy, SLC1A2 mutationAbstract
Seizures are a major neurologic disorder in infants and children. It can affect children at any age, from birth through adolescence. Early onset of seizures at birth or in the first few months of life can cause severe cerebral dysfunction. Also, recurrent and persistent seizures lead to severe cognitive and behavioral impairment in children. Hence, control of seizures is crucial for optimal neurodevelopment. Genetic aetiology of seizures is suspected in early onset recurrent seizures below one year of age, refractory to multiple anticonvulsants. Genetic testing in children with recurrent and therapy resistant seizures provides clue to aetiology, helps in treatment, has prognostic value. It also helps to estimate risk of seizure recurrence and helps avoid unnecessary investigations. We hereby report a case of early onset recurrent seizures with global developmental delay. Next generation sequencing revealed heterozygous missense mutation in SLC1A2 gene which is identified as an epileptic encephalopathy (EE) associated gene.
References
Camfield P, Camfield C. Incidence, prevalence and etiology of seizures and epilepsy in children. Epileptic Disord. 2015;17(2):117-23.
Berg AT, Langfitt JT, Testa FM, Levy SR, DiMario F, Westerveld M, et al. Residual cognitive effects of uncomplicated idiopathic and cryptogenic epilepsy. Epilepsy Behav. 2008;13(4):614-9.
Anderson V, Jacobs R, Spencer-Smith M, Coleman L, Anderson P, Williams J, et al. Does Early Age at Brain Insult Predict Worse Outcome? Neuropsychological Implications. J Pediatr Psychol. 2010;35(7):716-27.
Rahman MM, Fatema K. Genetic Diagnosis in Children with Epilepsy and Developmental Disorders by Targeted Gene Panel Analysis in a Developing Country. J Epilepsy Res. 2021;11(1):22.
Russo A, Gobbi G. A reflection on the role of genetics in the concept of “epileptic encephalopathy”, as emerged from the most recent ILEA classification of epilepsy. Ital J Pediatr. 2020;46(1):2.
Stafstrom CE, Carmant L. Seizures and Epilepsy: An Overview for Neuroscientists. Cold Spring Harb Perspect Med. 2015;5(6):a022426.
Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82.
Berg AT, Zelko FA, Levy SR, Testa FM. Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a prospective cohort study. Neurology. 2012;79(13):1384-91.
Holmes GL. Effect of Seizures on the Developing Brain and Cognition. Semin Pediatr Neurol. 2016;23(2):120-6.
Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-85.
Poduri A. When Should Genetic Testing Be Performed in Epilepsy Patients? Epilepsy Curr. 2017;17(1):16-22.
Møller RS, Larsen LHG, Johannesen KM, Talvik I, Talvik T, Vaher U et al. Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies. Mol Syndromol. 2016;7(4):210-9.
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. Am J Hum Genet. 2016;99(2):287-98.
Lemke JR, Syrbe S. Epileptic Encephalopathies in Childhood: The Role of Genetic Testing. Semin Neurol. 2015;35(3):310-22.
Kim K, Lee S-G, Kegelman TP, Su Z-Z, Das SK, Dash R, et al. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol. 2011;226(10):2484-93.
Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. J Neural Transm. 2014;121(8):799-817.
Stergachis AB, Pujol-Giménez J, Gyimesi G, Fuster D, Albano G, Troxler M et al. Recurrent SLC1A2 variants cause epilepsy via a dominant negative mechanism. Ann Neurol. 2019;85(6):921.
