Evidence map›Paper›PMID 41627953›Full record

ArticleEpilepsia2026

Characterizing early behavioral and social-emotional problems in young children with SCN1A+ Dravet syndrome: Findings from the ENVISION prospective natural history study.

Ingrid E Scheffer, M Scott Perry, Joseph Sullivan, Susana Boronat, James Wheless, Andreas Brunklaus, Linda Laux, Anup D Patel, Colin Roberts, Dennis Dlugos and 17 more

Registry-linked trialAbstract read
In one paragraph

Article in Epilepsia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04537832 (ENVISION), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04537832 terminatednot on this map

ENVISION: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies

TypeobservationalSponsorEncoded TherapeuticsRan2021 to 2023Enrolled58ConditionsDravet SyndromeArmsNo Intervention
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Ingrid E SchefferEpilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.ORCID https://orcid.org/0000-0002-2311-2174
M Scott PerryCook Children's Medical Center, Fort Worth, Texas, USA.ORCID https://orcid.org/0000-0002-1825-846X
Joseph SullivanUniversity of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0003-2081-8988
Susana BoronatHospital de la Santa Creu i Sant Pau, Barcelona, Spain.ORCID https://orcid.org/0000-0001-7096-5578
James WhelessLe Bonheur Children's Hospital, Memphis, Tennessee, USA.ORCID https://orcid.org/0000-0002-4735-3431
Andreas BrunklausSchool of Health and Wellbeing, Royal Hospital for Children, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0002-7728-6903
Linda LauxAnn & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Anup D PatelNationwide Children's Hospital, Columbus, Ohio, USA.ORCID https://orcid.org/0000-0001-9313-1541
Colin RobertsDoernbecher Children's Hospital, Portland, Oregon, USA.
Dennis DlugosChildren's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0003-3088-7645
Deborah HolderChildren's Hospital Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0001-5532-4764
Kelly KnuppChildren's Hospital Colorado, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-1967-0827
Matt LallasNicklaus Children's Hospital, Miami, Florida, USA.
Steven PhillipsMulticare Health System, Tacoma, Washington, USA.ORCID https://orcid.org/0009-0007-4704-2258
Eric SegalNortheast Regional Epilepsy Group and Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, New Jersey, USA.ORCID https://orcid.org/0000-0002-9986-6394
Dennis LalCleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.ORCID https://orcid.org/0000-0002-5173-9636
Elaine WirrellMayo Clinic, Rochester, Minnesota, USA.ORCID https://orcid.org/0000-0003-3015-8282
Sameer M ZuberiSchool of Health and Wellbeing, Royal Hospital for Children, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0002-4489-4697
Rebecca ShafferCincinnati Children's Hospital, Cincinnati, Ohio, USA.ORCID https://orcid.org/0000-0001-6935-4403
Mary WojnaroskiNationwide Children's Hospital, Columbus, Ohio, USA.ORCID https://orcid.org/0009-0006-5595-0419
Madison M BerlChildren's National Hospital, Washington, DC, USA.ORCID https://orcid.org/0000-0002-2469-1518
Sarah ChristensenEncoded Therapeutics, South San Francisco, California, USA.
Emma S JamesEncoded Therapeutics, South San Francisco, California, USA.ORCID https://orcid.org/0000-0003-2672-9652
Maria Candida VilaEncoded Therapeutics, South San Francisco, California, USA.ORCID https://orcid.org/0000-0003-4593-5822
Norman HuangEncoded Therapeutics, South San Francisco, California, USA.
Jacqueline S GofshteynEncoded Therapeutics, South San Francisco, California, USA.ORCID https://orcid.org/0000-0003-3354-6176
Salvador RicoEncoded Therapeutics, South San Francisco, California, USA.ORCID https://orcid.org/0000-0002-1508-8717

Funding

Encoded Therapeutics
6 · The paper itself

Abstract

objectiveDravet syndrome (DS) is the prototypic developmental and epileptic encephalopathy, characterized by drug-resistant seizures, developmental slowing, and many other morbidities. Detailed characterization of behavioral phenotypes and social-emotional skill development are limited.

methodsWe prospectively assessed behavioral and social-emotional problems in the ENVISION natural history study (NCT04537832) of children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at <5 years of age. Assessments every 3 months for up to 2 years included the Child Behavior Checklist (CBCL), Strengths and Difficulties Questionnaire (SDQ), Brief Infant-Toddler Social and Emotional Assessment (BITSEA), and Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3).

resultsFifty-eight children with DS enrolled at 16 sites worldwide. Problematic behaviors-inattention, aggressive or oppositional behaviors, and withdrawn and autistic behaviors-began before age 3 years, became more evident with age, and were clinically significant in many children by age 3-4 years. CBCL Total, Externalizing, and Internalizing Problems T-scores rose by approximately 3 points per year, and BITSEA Problem scale scores increased by 2.3 points annually (p = .002). SDQ Hyperactivity scores worsened over time (p = .013), whereas emotional difficulties remained stable. VABS-3 Socialization domain scores, which were already more than 1 SD below the normative mean at baseline, decreased further, particularly in younger participants. Correlation analyses showed that poorer communication abilities were associated with increased problematic behaviors (R = -.55 for CBCL Total Problems and VABS-3 Communication scores). Mixed-effects modeling identified age as the strongest predictor of worsening behavioral outcomes. SIGNIFICANCE: We found that behavioral and social-emotional problems are inherent components of DS that present in toddlerhood and worsen throughout early childhood. This highlights the need to diagnose and manage these issues early. Targeted therapy may alleviate the wide-ranging morbidities that are intrinsic to DS, including the social-emotional and behavior problems that frequently emerge.

Indexed as

Child Behavior DisordersEpilepsies, MyoclonicNAV1.1 Voltage-Gated Sodium ChannelProblem BehaviorChild, PreschoolEmotionsFemaleHumansInfantMaleProspective StudiesSocial BehaviorNAV1.1 Voltage-Gated Sodium ChannelSCN1A protein, humanBrief Infant‐Toddler Social and Emotional AssessmentChild Behavior ChecklistStrengths and Difficulties QuestionnaireVineland Adaptive Behavior Scales

Identifiers

PMID41627953
PMCPMC13179653

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.