A systematic review of adults with Dravet syndrome

Selvarajah, Arunan; Ali, Quratulain Zulfiqar; Marques, Paula; Rong, Marlene; Andrade, Danielle M.

doi:10.1016/j.seizure.2021.02.025

Cited by 44 publications

(38 citation statements)

References 82 publications

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“…Photosensitive epilepsy can also be observed in some patients with DS (17). In addition to the epileptic seizures, DS and other comorbidities that can be combined include ataxia, premature death, language, and motor development delay, cognitive impairment, sleep disorders, ASD, and SUDEP, which seriously affect the quality of life of the patients and pose a heavy economic burden to the family and society (18)(19)(20)(21)(22)(23).…”

Section: Dravet Syndromementioning

confidence: 99%

SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

Ding

Tian

et al. 2021

Front. Neurol.

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Background:SCN1A is one of the most common epilepsy genes. About 80% of SCN1A gene mutations cause Dravet syndrome (DS), which is a severe and catastrophic epileptic encephalopathy. More than 1,800 mutations have been identified in SCN1A. Although it is known that SCN1A is the main cause of DS and genetic epilepsy with febrile seizures plus (GEFS+), there is a dearth of information on the other related diseases caused by mutations of SCN1A.Objective: The aim of this study is to systematically review the literature associated with SCN1A and other non-DS-related disorders.Methods: We searched PubMed and SCOPUS for all the published cases related to gene mutations of SCN1A until October 20, 2021. The results reported by each study were summarized narratively.Results: The PubMed and SCOPUS search yielded 2,889 items. A total of 453 studies published between 2005 and 2020 met the final inclusion criteria. Overall, 303 studies on DS, 93 on GEFS+, three on Doose syndrome, nine on the epilepsy of infancy with migrating focal seizures (EIMFS), six on the West syndrome, two on the Lennox–Gastaut syndrome (LGS), one on the Rett syndrome, seven on the nonsyndromic epileptic encephalopathy (NEE), 19 on hemiplegia migraine, six on autism spectrum disorder (ASD), two on nonepileptic SCN1A-related sudden deaths, and two on the arthrogryposis multiplex congenital were included.Conclusion: Aside from DS, SCN1A also causes other epileptic encephalopathies, such as GEFS+, Doose syndrome, EIMFS, West syndrome, LGS, Rett syndrome, and NEE. In addition to epilepsy, hemiplegic migraine, ASD, sudden death, and arthrogryposis multiplex congenital can also be caused by mutations of SCN1A.

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Section: Dravet Syndromementioning

confidence: 99%

SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

Ding

Tian

et al. 2021

Front. Neurol.

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“…Tonic seizures occurring during sleep, with the potential to disrupt the sleep cycle, are characteristic of LGS [48]. DS children and adults have more nighttime awakenings, reflective of poor quality of sleep [25]. SCNA1 mutations dysregulate neurological sleep networks [8,66], as demonstrated in a mouse model, in which Na V 1.1 channels encoded by SCN1A are expressed in the GABAergic neurons in the hypothalamus, thalamic reticular nucleus, and cortex [69].…”

Section: Gitiaux Et Al Proposed That To Understand Gait Disturbance W E S H O U L D C O N S I D E R D S a S A S O D I U M C H A N N E L Imentioning

confidence: 99%

“…Intellectual disability (ID) is a comorbidity of DS, but it is still unclear if ID results from damage caused by seizures, the abnormal levels of Na v 1.1 protein, the use of inappropriate medications, such as sodium channel inhibitors, or a combination of these factors [25]. DS typically presents in the first year of life in children with no pre-existing developmental problems [3,21,26,27].…”

Section: Dravet Syndromementioning

confidence: 99%

“…Whereas the nature of seizures can change and seizure burden can decrease, the burden of comorbidities in DS and LGS does not improve and increases with age [25,29,48,50,59]. Although seizures remain a prominent problem, cognitive, behavioral, and physical comorbidities can eclipse seizures as a higher management priority in adolescent and adult patients with LGS, reflecting the importance of education, independence, and the ability to work, interact with peers, and form relationships [15,48,59].…”

Section: Impact Of Comorbidities On Patients and Caregiversmentioning

confidence: 99%

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Comorbidities in Dravet Syndrome and Lennox–Gastaut Syndrome

Marchese

Cappelletti

Filippini³

et al. 2021

SN Compr. Clin. Med.

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This study aims to describe the main cognitive and behavioral comorbidities of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), their impact on the health-related quality of life (QOL) of patients and their caregivers, and provide a summary of the neuropsychological tools available for the evaluation of these comorbidities. The cognitive and behavioral comorbidities in patients with DS and LGS have a profound effect on the QOL of affected individuals and their caregivers and, as patients grow, tend to surpass the impact of the seizures. DS is a genetic condition associated with loss-of-function mutations in the SCNA1 sodium channel gene; LGS is an etiologically heterogeneous condition that is often secondary to structural brain abnormalities. The first seizures associated with DS typically present in the first year of life, and developmental delay becomes progressively evident thereafter. LGS usually starts between the ages of 3 and 8 years, with cognitive impairment becoming clinically evident in most patients within 5 years from the onset. In both DS and LGS, cognitive impairment is generally moderate to severe and is often accompanied by behavioral problems such as hyperactivity and inattention. In addition to optimal seizure control, regular assessment and active management of cognitive and behavioral comorbidities are required to meet the complex needs of patients with DS or LGS.

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“…For example, a genetic cause has been identified in more than 90% of patients with Dravet syndrome, while only 65 to 75% of LGS cases have a clear identifiable cause (which can include structural, metabolic or genetic causes). 13 , 14 , 47 All patients with LGS in this cohort ( n = 6) had intractable epilepsy, including tonic seizures amongst other types, ID, and EEGs showing generalized slow spike and waves and generalized paroxysmal fast activity during sleep. WGS identified clinically relevant genetic variants in four of the six patients with LGS (66.6%).…”

Section: Discussionmentioning

confidence: 99%

Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox–Gastaut syndrome

Qaiser

Sadoway

Yin

et al. 2021

Brain Communications

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Epilepsies are a group of common neurological disorders with a substantial genetic basis. Despite this, the molecular diagnosis of epilepsies remains challenging due to its heterogeneity. Studies utilizing whole genome sequencing may provide additional insights into genetic causes of epilepsies of unknown etiology. Whole genome sequencing was used to evaluate a cohort of adults with unexplained developmental and epileptic encephalopathies (n = 30), for whom prior genetic tests, including whole exome sequencing in some cases, were negative or inconclusive. Rare single nucleotide variants, insertions/deletions, copy number variants and tandem repeat expansions were analyzed. Seven pathogenic or likely pathogenic single nucleotide variants, and two pathogenic deleterious copy number variants were identified in nine patients (32.1% of the cohort). One of the copy number variants, identified in a patient with Lennox-Gastaut syndrome, was too small to be detected by chromosomal microarray techniques. We also identified two tandem repeat expansions with clinical implications in two other patients with Lennox-Gastaut syndrome: a CGG repeat expansion in the 5’untranslated region of DIP2B, and a CTG expansion in ATXN8OS (previously implicated in spinocerebellar ataxia type 8). Three patients had KCNA2 pathogenic variants. One of them died of sudden unexpected death in epilepsy. The other two patients had, in addition to a KCNA2 variant, a second de novo variant impacting potential epilepsy-relevant genes (KCNIP4 and UBR5). Overall, whole genome sequencing provided a genetic explanation in 32.1% of the total cohort. This is also the first report of coding and non-coding tandem repeat expansions identified in patients with Lennox-Gastaut syndrome. This study demonstrates that using whole genome sequencing, the examination of multiple types of rare genetic variation, including those found in the non-coding region of the genome, can help resolve unexplained epilepsies.

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A systematic review of adults with Dravet syndrome

Cited by 44 publications

References 82 publications

SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

Comorbidities in Dravet Syndrome and Lennox–Gastaut Syndrome

Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox–Gastaut syndrome

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