Biallelic <i>SCN2A</i> Gene Mutation Causing Early Infantile Epileptic Encephalopathy: Case Report and Review

AlSaif, Shahad; Umair, Muhammad; Alfadhel, Majid

doi:10.1177/1179573519849938

Cited by 11 publications

(10 citation statements)

References 92 publications

(116 reference statements)

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“…There was a range of DD and/or ID within this cohort, from mild to profound in‐keeping with previous case series (Alsaif et al, 2019; Schwarz et al, 2019). There was a range of seizure phenotypes reported.…”

Section: Discussionsupporting

confidence: 89%

Further delineation of phenotypic spectrum of SCN2A‐related disorder

Richardson

Baralle

Bennett

et al. 2021

American J of Med Genetics Pt A

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SCN2A‐related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype–genotype association in SCN2A‐related disorders was further delineated by collecting detailed clinical and molecular characteristics. Using previously proposed genotype–phenotype hypotheses based on variant function and position, the potential of phenotype prediction from the variants found was examined. Patients were identified through the Deciphering Developmental Disorders study and gene matching strategies. Phenotypic information and variant interpretation evidence were collated. Seventeen previously unreported patients and five patients who had been previously reported (but with minimal phenotypic and segregation data) were included (10 males, 12 females; median age 10.5 years). All patients had developmental delays and the majority had intellectual disabilities. Seizures were reported in 15 of 22 (68.2%), four of 22 (18.2%) had autism spectrum disorder and no patients were reported with episodic ataxia. The majority of variants were de novo. One family had presumed gonadal mosaicism. The correlation of the use of sodium channel‐blocking antiepileptic drugs with phenotype or genotype was variable. These data suggest that variant type and position alone can provide some predictive information about the phenotype in a proportion of cases, but more precise assessment of variant function is needed for meaningful phenotype prediction.

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Section: Discussionsupporting

confidence: 89%

Further delineation of phenotypic spectrum of SCN2A‐related disorder

Richardson

Baralle

Bennett

et al. 2021

American J of Med Genetics Pt A

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“…Very rarely, cases of homozygous, biallelic, SCN2A patients have been described, generally affected epileptic encephalophaty. 55 The risk to family members is similar to that of other monogenic epilepsies:…”

Section: Genetic Counselingmentioning

confidence: 94%

SCN2A and Its Related Epileptic Phenotypes

Sullo

Pasquetti

Patanè

et al. 2021

Journal of Pediatric Neurology

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Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A-related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A–benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A-BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A-related epilepsies have not shown a clear genotype–phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no “standardized” treatment for SCN2A-related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

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“…We describe the second documented homozygous SCN2A mutation causing EIEE in autosomal recessive inheritance, the first case was published three months before (9). All previous patients were reported having a heterozygous SCN2A variant in either dominant or de novo fashion.…”

Section: Discussionmentioning

confidence: 89%

Homozygous SCN2A gene mutation causing early infantile epileptic encephalopathy: The second case in literature

Yılmaz

2019

Med Sci Discov

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Objective: Early infantile epileptic encephalopathy type11 (EIEE) generally known as an autosomal dominant inherited disease caused by the voltage-gated sodium channel neuronal type 2 alpha subunit (Navα1.2) encoded by the SCN2A gene mutations. The clinic of the disease is variable. Herein we report the second case with a homozygous missense mutation of the SCN2A gene (c.1588 G>T). Material and methods: NGS gene panel including the SCN2A gene from genomic DNA extracted from peripheral blood using a commercially available kit and quantified using standard methods. Illumina miseq analysis platform was used for this purpose, we performed analysis of coding regions and exon-intron boundaries and the data was analyzed by IGV. Results: The results confirmed by sanger sequencing show us an SCN2A (NM_001040142) c.1588 G>T homozygote mutation. Conclusion: This shows us more clinical and molecular studies need for SCN2A associated disease pathogenesis

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Biallelic SCN2A Gene Mutation Causing Early Infantile Epileptic Encephalopathy: Case Report and Review

Cited by 11 publications

References 92 publications

Further delineation of phenotypic spectrum of SCN2A‐related disorder

Further delineation of phenotypic spectrum of SCN2A‐related disorder

SCN2A and Its Related Epileptic Phenotypes

Homozygous SCN2A gene mutation causing early infantile epileptic encephalopathy: The second case in literature

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