Research Opportunities:

In addition to the opportunity to participate in research with Simons VIP, you may be interested in other opportunities.

  • TIGER Study: The University of Washington’s Autism Center is performing a study to better understand the medical, learning, and behavioural features of individuals with changes in SCN2A.  Click here to learn more about this opportunity.

Research Article Summaries: 

Below, we've summarized several research articles that include information about SCN2A. We hope you find this information helpful! As we learn more from children who have these gene changes, we expect this list of resources and information to grow.

  • Schwarz et al., (2016)Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

    Linked with signaling in the brain, genetic changes (mutations) in the SCN2A gene have been associated with various degrees of epilepsy, including neonatal-infantile seizures. In this research study, Schwarz and colleagues describe four cases of individuals with mutations in the SCN2A gene. These individuals experienced seizures early in their lives as well as other episodic symptoms that began later in childhood. These “episodes” occurred sporadically, with each individual having periods where they experienced no symptoms alternating with periods where the symptoms presented. Episodic symptoms varied in frequency and severity between the four individuals (see the table below for additional information). One case had been previously identified by the researchers, but the other three cases were newly identified via clinical observations and subsequent genetic testing.

    All four individuals experienced their first seizure before they were one month old. Three individuals were considered “seizure-free” before their first birthday. The fourth individual was considered seizure-free at the age of 13 months; however, he did experience isolated seizures at ages 3, 6, and 14. While the individuals were reported to be seizure-free, all four presented with episodes of ataxia (coordination issues) and three of the four individuals experienced headaches, slurred speech, and balance issues. The frequency and duration of these episodes varied between individuals. Some of the researchers’ observations are further summarized below. 

  • Allen et al., 2015Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion

    Whole-exome sequencing was done on 50 children with unexplained early onset epileptic encephalopathies (EOEEs), aiming to target epilepsy-associated genes. Having an epileptic encephalopathy can impact neurological development and can be linked to cognitive and behavioral disturbances. This study identified disease causing genetic changes in 11 children, one of whom was found to have a new (de novo) variant in the SCN2A gene. The child exhibited brain abnormalities from birth, severe intellectual disability (ID), abnormal muscle tone, and seizures while awake and asleep. Future studies aimed at developing a list of genes associated with EOEEs through whole exome sequencing will allow clinicians to provide patient-specific therapies and improve overall treatment. 

  • Tavassoli et al., 2014 De novo SCN2A splice site mutation in a boy with autism spectrum disorder

    This article details behaviors and clinical findings in a seven-year-old boy with a SCN2A genetic change (mutation). As a gene highly expressed in the brain, mutations in SCN2A have been linked to autism, as well as intellectual disability, ataxia, and epilepsy. The individual in this paper exhibited a de novo, or “new,”mutation of the SCN2A gene which results in a portion of the gene being deleted. Over a period of four years, researchers noted that the child exhibited distinct facial features, social and language impairments, and motor delays. He was clinically diagnosed with autism spectrum disorder (ASD). Of interest, he was not found to have any history of seizures (although late onset cannot be ruled out). While the boy’s specific mutation is not currently linked to autism, this study, as well as future research, may suggest that it may be a contributing factor. 

  • Srivastava et al., 2014 - Clinical Whole Exome Sequencing in Child Neurology Practice
    78 individuals with developmental delay (DD), intellectual disability (ID), cerebral palsy (CP), or autism (ASD), had whole exome sequencing as part of this study. One individual in the study was identified to have a SCN2A mutation. The individual described in this study (age 18 at the time of genetic diagnosis) had never been diagnosed with either intellectual disability or autism, but was noted to have epileptic encephalopathy.

  • Epi4K Consortium et al., 2013 - De novo mutations in the classic epileptic encephalopathies
    The exomes (1% of the entire genome) of 264 “trios” (child and both parents) were sequenced to seek a genetic cause for infantile spasms and another seizure disorder called “Lennox-Gastaut syndrome.” This study identified over 300 de novo (not inherited from either parent) gene changes in 9 genes, including 2 patients with variants in SCN2A. More research and information is needed to determine the association between SCN2A and Lennox-Gastaut syndrome.

  • Carvill et al., 2013 - Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
    This study sought to characterize the genetic origin of children who have seizure disorders. While has been previously shown that changes in SCN2A can cause seizures very early in life, the children in this study had differences in the times in which their seizures began. For some, seizures began within the first few hours of life (3 children), and for others, they began after a couple of weeks (2 children). The five children with SCN2A changes in this study all had some degree of intellectual involvement.

  • Rauch et al., 2012 - Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study
    The SCN2A gene plays an important role in the brain’s development. Changes in this gene have been previously linked to seizure disorders and significant intellectual differences. In this study, children with SCN2A gene changes did not have a seizure disorder. Rather, these children had intellectual differences, behavior issues, and subtle differences in their facial features.One child with a change in SCN2A also exhibited a few of the features of autism. Changes in this gene are not often inherited.

  • deLigt et al., 2012 - Diagnostic exome sequencing in persons with severe intellectual disability
    In this study, 100 patients with severe intellectual disability (and their unaffected parents) underwent exome sequencing to attempt to identify a genetic cause for their diagnosis. Further analysis was performed for five genes that have been associated with intellectual disability (DYNC1H1, GATAD2B, ASH11, KIFSC and CTNNB1) in 765 additional patients with intellectual disability. One individual was identified to have some degree of intellectual disability, behavior problems, epilepsy, sleep disturbances, stereotypic behaviors (which is one of the features of autism).

You can also visit SFARI's website to see information written for researchers about this gene. SFARIgene: SCN2A

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