ArticleEpilepsia open2025
SCN1A gain of function effects in Dravet syndrome: Insights into clinical phenotypes and therapeutic implications.
Article in Epilepsia open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- ADNP missense variant p.C687R disrupts chromatin regulation and GABAergic differentiation in Helsmoortel-Van der Aa syndrome.Molecular autism · 2026Article
- [Adeno-associated virus-mediated gene therapy for genetic epilepsy: prospects and challenges].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders.International journal of molecular sciences · 2025Review
- Reply to Letter to the Editor regarding the article "SCN1A gain of function effects in Dravet syndrome: Insights into clinical phenotypes and therapeutic implications".Epilepsia open · 2025Article
- To the editors: SCN1A gain-of-function effects in Dravet syndrome: Insights into clinical phenotypes and therapeutic implications.Epilepsia open · 2025Article
- SCN1A gain of function effects in Dravet syndrome: Insights into clinical phenotypes and therapeutic implications.Epilepsia open · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
A large number of cases with Dravet syndrome (DS) has been attributed to SCN1A loss of function (LOF), whereas SCN1A gain-of-function (GOF) causes early infantile developmental and epileptic encephalopathy (EIDEE) and familial hemiplegic migraine 3. We retrospectively analyzed 37 individuals with SCN1A pathogenic variants at our institute between January 2012 and October 2024 to investigate phenotype-function correlations. Variant functions were classified as LOF, GOF, or mixed, based on existing patch-clamp data, paralog sodium channel experimental findings, and in silico prediction tools. Clinical characteristics, antiseizure medication (ASM) responses, and variant location were compared. Nine variants were novel. One variant with insufficient data for functional prediction was excluded. Of the 36 cases with predictable functions, five cases (14%) were classified as GOF/mixed (DS = 4, EIDEE = 1) and 31 (86%) as LOF (DS = 31). GOF/mixed-DS had earlier epilepsy onset but otherwise resembled LOF-DS. Sodium channel blocking ASMs (SCB-ASMs) did not exacerbate seizures in GOF/mixed DS cases, with carbamazepine reducing seizures in one case. GOF/mixed variants clustered in the intracellular S6 segment, whereas LOF variants clustered in the S5-S6 pore loop. These findings highlight a potential GOF effect for certain DS cases, suggesting that SCB-ASMs may be effective for GOF/mixed DS. This underscores the importance of functional characterization for tailored therapy, warranting further research to confirm and extend these results. PLAIN LANGUAGE SUMMARY: Dravet syndrome is a severe epilepsy that usually begins in infancy and is linked to changes in a gene called SCN1A. Most cases are caused by gene changes that reduce function, but in some cases, the gene may become overactive. In this study, we found that some patients with Dravet syndrome had these overactive changes and still showed typical symptoms. We found that people with overactive SCN1A function might respond differently to certain medications.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.