Infantile Epileptic Encephalopathy With Multiple Genetic Mutations: How Important are Variants of Undetermined Significance?

Almomen, Momen; Rho, Jong M.; Scantlebury, Morris H.

doi:10.1016/j.spen.2018.04.002

Cited by 2 publications

(2 citation statements)

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“…The types of CDKL5 variants may lead to differing severities of clinical phenotypes, and a deletion variant may exhibit a higher disease burden. In addition, one patient presented with a phenotype that might overlap with Rett syndrome, which was associated with MECP2 phosphorylation ( 22 ), but this feature was not detected in the WS patient. The WS patient showed a good response for a honeymoon period of 1 year without cognitive improvement.…”

Section: Discussionmentioning

confidence: 99%

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

et al. 2021

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Objective: The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE).Methods: NGS was performed on 50 children with unexplained EIEE. The clinical profiles of children with pathogenic variants were characterised and analysed in detail. Conservation analysis and homology modelling were performed to predict the impact of STXBP1 variant on the protein structure.Results: Pathogenic variants were identified in 17 (34%) of 50 children. Sixteen variants including STXBP1 (n = 2), CDKL5 (n = 2), PAFAH1B1, SCN1A (n = 9), SCN2A, and KCNQ2 were de novo, and one (PIGN) was a compound heterozygous variant. The phenotypes of the identified genes were broadened. PIGN phenotypic spectrum may include EIEE. The STXBP1 variants were predicted to affect protein stability.Significance: NGS is a useful diagnostic tool for EIEE and contributes to expanding the EIEE-associated genotypes. Early diagnosis may lead to precise therapeutic interventions and can improve the developmental outcome.

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Section: Discussionmentioning

confidence: 99%

Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

et al. 2021

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“…It is caused by dominant loss of function variants in the X-linked CDKL5 gene, which plays an important role in brain development [2]. Clinically often found in girls, common features of CDKL5 deficiency are drug-resistant intractable epilepsy that develops within the first three months after birth and a severe psychomotor retardation [3,4]. Here, we report the case of a girl with clinical diagnosis of early myoclonic encephalopathy (EME) in which a CDKL5 mutation was revealed at 14 years of age.…”

Section: Introductionmentioning

confidence: 99%