Generalized Epilepsy with Febrile Seizures Plus (GEFS+): Comprehensive Disease Characteristics Report

Target Disease

• Disease name: Generalized epilepsy with febrile seizures plus (GEFS+)
• Category: Mendelian (classically autosomal dominant), with evidence for modifier/polygenic contributions
• MONDO ID: MONDO:0018214 (via Open Targets disease mapping) (OpenTargets Search: Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+)

1. Disease information

1.1 Concise overview

GEFS+ is a familial epilepsy syndrome characterized by febrile seizures (FS) and “febrile seizures plus” (FS+) with variable occurrence of afebrile seizures (generalized and/or focal), showing incomplete penetrance and variable expressivity across affected relatives. (agathe2025polygenicriskscore pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

A core operational definition for FS+ used in classic and modern sources is persistence of fever-triggered seizures beyond age 6 years and/or association with afebrile generalized tonic-clonic seizures. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2, agathe2025polygenicriskscore pages 1-2)

1.2 Key identifiers (available in retrieved evidence)

Table: This table summarizes the key identifiers and commonly used synonyms for generalized epilepsy with febrile seizures plus. It is useful for harmonizing disease terminology across knowledge-base, ontology, and literature sources.

Notes on identifier gaps: ICD-10/ICD-11 and MeSH identifiers were not retrieved in the current evidence corpus; they are therefore not reported here to avoid speculation. (escayg2001anovelscn1a pages 8-8, OpenTargets Search: Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+)

1.3 Common synonyms / alternative names

Frequently used synonyms include “genetic epilepsy with febrile seizures plus” and “epilepsy with febrile seizures plus.” (agathe2025polygenicriskscore pages 1-2, li2024gabrg2mutationsin pages 1-2)

1.4 Evidence provenance (individual-level vs aggregated)

• Aggregated syndrome-level resources and reviews: 2024 disease-focused review of GABRG2 in GEFS+ (Journal of Translational Medicine) provides consolidated definitions, variant classes, and mechanistic hypotheses. (li2024gabrg2mutationsin pages 1-2)
• Individual/family-level primary genetic studies: large pedigrees and linkage/functional studies (e.g., SCN1B in 1998 and SCN1A in 2001) define inheritance and establish causal variants. (wallace1998febrileseizuresand pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

2. Etiology

2.1 Disease causal factors (primary)

GEFS+ is primarily a genetic epilepsy syndrome with prominent contributions from ion channel and synaptic genes, particularly voltage-gated sodium channel genes and GABA-A receptor subunit genes. (li2024gabrg2mutationsin pages 1-2, wallace1998febrileseizuresand pages 1-2)

Classic genetic evidence established SCN1B (Nav β1 subunit) as a GEFS+ gene through linkage to 19q13.1 and a co-segregating missense variant with functional loss of β1 modulation. (wallace1998febrileseizuresand pages 1-2)

Subsequently, SCN1A (Nav1.1 α subunit) was established as a major locus (GEFS2/2q) with multiple missense mutations identified in familial cases, and estimates of mutation frequencies in familial cohorts. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

2.2 Risk factors

Genetic risk factors (causal genes)

Core genes consistently highlighted as causative/major contributors include SCN1A, SCN1B, and GABRG2. (agathe2025polygenicriskscore pages 1-2, li2024gabrg2mutationsin pages 1-2)

Additional genes supported in aggregated disease–target evidence include STX1B, SLC32A1, HCN1/HCN2, SCN9A, PRRT2, and GABRD (evidence anchored to PubMed IDs listed in Open Targets). (OpenTargets Search: Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+)

Environmental/physiologic triggers

Fever and temperature elevation are key triggers (by definition), and temperature-dependence has been discussed since early family-based work (“possible temperature dependence” noted in classic SCN1B family) and is consistent with later model-system literature emphasizing heat-induced seizures in related channelopathies. (wallace1998febrileseizuresand pages 1-2, gyamfi2025voltagegatedsodiumchannel pages 14-16)

2.3 Protective factors

Protective genetic or environmental factors were not explicitly identified in the retrieved evidence corpus; current evidence emphasizes modifier effects rather than clearly protective alleles. (agathe2025polygenicriskscore pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

2.4 Gene–environment interactions

Modern commentary explicitly frames GEFS+ as an autosomal dominant disease with incomplete penetrance and variable expressivity, where outcome variability may reflect interactions between a pathogenic variant and other genetic factors (and potentially environmental factors). (agathe2025polygenicriskscore pages 1-2)

A 2025 eBioMedicine commentary on a 2024 GEFS+ family study reports that relatives with more severe phenotypes had higher polygenic risk scores, supporting a model where polygenic background modifies expressivity of rare pathogenic variants. (agathe2025polygenicriskscore pages 1-2)

3. Phenotypes (with HPO suggestions)

Table: This table summarizes the supported GEFS+ phenotypic spectrum, onset/remission timing, and available frequencies from classic and recent evidence. It is useful for mapping clinical features to HPO terms and capturing temporal disease characteristics for a knowledge base.

Key spectrum concepts include: - FS and FS+ at the mild end, with variable additional afebrile seizure types (absence, myoclonic, atonic). (lerche2001generalizedepilepsywith pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2) - A spectrum extending to more severe developmental and epileptic encephalopathy (DEE) phenotypes such as Dravet syndrome and myoclonic-atonic epilepsy. (agathe2025polygenicriskscore pages 1-2)

4. Genetic / molecular information

4.1 Causal genes (supported in retrieved evidence)

A gene-centric synthesis of major and additional supported genes is provided below.

Table: This table summarizes the principal genes currently supported in the retrieved evidence for GEFS+ and the main mechanistic themes linking them to disease. It combines classic discovery papers with recent reviews and target-association evidence to show how sodium-channel, GABAergic, and synaptic genes converge on neuronal hyperexcitability.

4.2 Pathogenic variant classes and examples

• SCN1B: C121W / p.Cys121Trp is the classic co-segregating familial GEFS+ variant, absent in controls and shown to impair β1 function in a Xenopus oocyte co-expression system. (wallace1998febrileseizuresand pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)
• SCN1A: multiple missense variants, including variants in conserved S4 segments (e.g., T875M, R1648H) and additional familial variants (D188V, V1353L, I1656M) with reported frequency estimates in familial cohorts. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)
• GABRG2: the 2024 review summarizes missense, nonsense, frameshift, point, and splice-site variants, with example nomenclature including p.Met199Val, R136*, Q390*, W429*, p.Val462fs*33, and IVS6+2T>G. (li2024gabrg2mutationsin pages 1-2)

Visual evidence (variant catalog)

Cropped regions of Li et al. (2024) Table 2 summarize GABRG2 variant types and associated phenotypes/mechanisms. (li2024gabrg2mutationsin media a0660f7d, li2024gabrg2mutationsin media 969b1bdb, li2024gabrg2mutationsin media 78a53eaa, li2024gabrg2mutationsin media 591accf4)

4.3 Modifier genes / polygenic background

A 2025 eBioMedicine commentary summarizes evidence that polygenic risk score (PRS) can stratify severity among relatives carrying pathogenic variants in GEFS+ families, consistent with polygenic modification of a primarily Mendelian syndrome. (agathe2025polygenicriskscore pages 1-2)

4.4 Epigenetic information / chromosomal abnormalities

No GEFS+-specific epigenetic signatures or recurrent chromosomal abnormalities were retrieved in the current evidence corpus. (li2024gabrg2mutationsin pages 1-2)

5. Environmental information

Beyond fever/temperature as a key physiologic trigger, additional environmental contributors (toxins, lifestyle) were not systematically addressed in the retrieved GEFS+-focused sources. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2, li2024gabrg2mutationsin pages 1-2)

6. Mechanism / pathophysiology

6.1 Causal chain (genotype → cellular dysfunction → network hyperexcitability → seizures)

SCN1B: A β1-subunit loss-of-function variant disrupts modulation of sodium-channel gating/inactivation, which is hypothesized to increase sodium influx, depolarize membranes, and promote hyperexcitability. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2, wallace1998febrileseizuresand pages 1-2)

SCN1A: Missense variants in conserved channel domains (including S4 voltage-sensor segments) are proposed to alter gating/inactivation, contributing to seizure susceptibility and fever sensitivity in the GEFS+/SCN1A spectrum. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

GABRG2: GEFS+ variants reduce GABA-A receptor function at the cell membrane and implicate receptor trafficking as a central mechanism (“γ2 subunit plays a special role in receptor trafficking”). (li2024gabrg2mutationsin pages 1-2)

6.2 Immune / inflammatory contributions (emerging, preclinical)

A recent therapeutics-oriented review highlights inflammatory mediators (e.g., IL-6, TNFα) as associated with seizure recurrence and describes suppression of seizures in model systems by blocking the STAT3–IL-6 pathway or using anti-IL-6 monoclonal antibody approaches, supporting immune-modulatory hypotheses relevant to fever-triggered epilepsies. (gyamfi2025voltagegatedsodiumchannel pages 14-16)

6.3 Ontology suggestions

GO biological process (suggestions): - regulation of membrane depolarization / action potential firing - synaptic transmission, GABAergic - ion transmembrane transport - regulation of synaptic vesicle exocytosis

Cell Ontology (CL) cell types (suggestions): - GABAergic interneuron - glutamatergic pyramidal neuron - microglial cell (given inflammatory pathway discussions)

(These are ontology suggestions consistent with mechanisms described in the cited evidence; they are not asserted as direct annotations unless formally demonstrated in the cited studies.) (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2, li2024gabrg2mutationsin pages 1-2, gyamfi2025voltagegatedsodiumchannel pages 14-16)

7. Anatomical structures affected

Primary involvement is the central nervous system, particularly neuronal networks mediating excitation/inhibition balance.

UBERON suggestions: - UBERON:0000955 brain - UBERON:0001017 central nervous system

Relevant cellular compartments include ion-channel/receptor localization at the plasma membrane and receptor trafficking pathways. (li2024gabrg2mutationsin pages 1-2, wallace2001neuronalsodiumchannelalpha1subunit pages 1-2)

8. Temporal development

Typical temporal features include: - Onset: fever-associated generalized tonic–clonic seizures commonly reported from 3 months to 6 years in a recent review, and febrile seizures are classically concentrated in early childhood. (li2024gabrg2mutationsin pages 1-2, wallace1998febrileseizuresand pages 1-2) - Course: many cases remit in childhood (one early family average seizure termination ~11 years), but FS+ may persist longer (remission reported up to adulthood in cohort summaries). (li2024gabrg2mutationsin pages 1-2, li2024gabrg2mutationsin pages 6-7)

9. Inheritance and population

9.1 Inheritance

GEFS+ is classically autosomal dominant with incomplete penetrance and variable expressivity. (agathe2025polygenicriskscore pages 1-2, li2024gabrg2mutationsin pages 1-2)

Quantitative penetrance estimates reported in classic studies include ~60% penetrance in some pedigrees and ~80% penetrance in one family-based report. (wallace1998febrileseizuresand pages 1-2, lerche2001generalizedepilepsywith pages 1-2)

9.2 Epidemiology

Robust GEFS+-specific prevalence/incidence estimates were not retrieved in the current evidence corpus.

However, febrile seizures in the general pediatric population are common, reported as approximately 3% of children in a classic genetics paper and 2–4% in another summary source. (wallace1998febrileseizuresand pages 1-2, meyer2024characterizationsofa pages 9-12)

10. Diagnostics

10.1 Clinical evaluation

Clinical work-up commonly includes: - Seizure semiology and history (including fever association, persistence beyond age 6) - EEG and neuroimaging (CT/MRI) as part of syndrome characterization (no GEFS+-specific performance metrics were retrieved). (meyer2024characterizationsofa pages 9-12)

10.2 Genetic testing

A practical diagnostic pathway supported by a large clinical cohort: - Targeted next-generation sequencing (TNGS) epilepsy panels as a first step in syndromes with major genes (explicitly including GEFS+), with a reported 16% yield in GEFS+ (62 patients) in a 1000-patient pediatric epilepsy cohort. (barcia2025geneticetiologieswith pages 2-4) - WES/WGS as second-tier testing when panel testing is negative in likely Mendelian syndromes; broader pediatric epilepsy practice shows WGS/WES can deliver substantial yield (example: 37.9% molecular diagnosis rate in a 733-family cohort, not GEFS+-specific). (barcia2025geneticetiologieswith pages 1-2)

11. Outcomes / prognosis

GEFS+ is often described as relatively benign in many families but spans a spectrum that includes severe epilepsies (DEE/Dravet/myoclonic-atonic epilepsy). (agathe2025polygenicriskscore pages 1-2)

Natural history data retrieved include: - seizure cessation in mid-childhood in one classic family (average ~11 years), but FS+ remission can extend into adulthood in cohort summaries (6–34 years). (li2024gabrg2mutationsin pages 1-2, li2024gabrg2mutationsin pages 6-7)

SUDEP risk: SUDEP-specific statistics were not retrieved in the current evidence corpus and are not reported here. (agathe2025polygenicriskscore pages 1-2)

12. Treatment

12.1 Current clinical management (anti-seizure medications; supportive care)

GEFS+ treatment largely follows general epilepsy standards (anti-seizure medications, rescue plans, and avoidance/management of fever triggers), but a recent GEFS+ review notes that “there are no particularly effective antiepileptic drugs for the minority of GEFS+ families,” reflecting heterogeneity and treatment-refractory subsets. (li2024gabrg2mutationsin pages 6-7)

12.2 Precision medicine and real-world implementation

A precision-diagnostics study of pediatric epilepsy demonstrates that molecular diagnoses can drive gene-directed therapy decisions (11/55 children), including children with SCN1A variants, illustrating real-world clinical implementation of genotype-informed care even when GEFS+ itself is not uniformly treated with a single gene-specific therapy. (andjelkovic2024characterizationof13 pages 1-2)

12.3 Advanced therapeutics (latest research; 2023–2024 priority)

A major 2024–initiated gene therapy clinical program for the SCN1A spectrum: - ETX101 (Encoded Therapeutics) Phase 1/2 trial NCT05419492 (Recruiting; start 2024-05-14) uses an rAAV9-delivered engineered transcription factor intended to increase SCN1A transcription in inhibitory neurons; primary efficacy endpoint is percent change in monthly countable seizure frequency from baseline to Weeks 5–52; estimated enrollment 47 with age-stratified cohorts. (NCT05419492 chunk 1)

12.4 Structured intervention summary (with MAXO suggestions)

Table: This table summarizes current clinical and translational applications relevant to GEFS+ and the SCN1A-related epilepsy spectrum, including diagnostic strategies, emerging gene therapy trials, and preclinical mechanism-based treatments. It is useful for linking interventions to evidence type, quantitative details, and MAXO-style action annotations.

13. Prevention

No GEFS+-specific primary prevention strategy was retrieved beyond general epilepsy/febrile seizure best practices (fever management, seizure action plans) and genetic counseling for autosomal dominant familial risk with incomplete penetrance. (agathe2025polygenicriskscore pages 1-2, wallace1998febrileseizuresand pages 1-2)

14. Other species / natural disease

Naturally occurring GEFS+-analog diseases in non-human species were not retrieved in the current evidence corpus. (gyamfi2025voltagegatedsodiumchannel pages 14-16)

15. Model organisms

Evidence in the retrieved corpus supports several model systems relevant to GEFS+ mechanisms: - Xenopus oocyte co-expression electrophysiology used to show impaired SCN1B β1-subunit function for the classic GEFS+ variant. (wallace1998febrileseizuresand pages 1-2) - Mouse models referenced in the context of fever-associated epilepsy and synaptic/threshold changes after complex febrile seizures; and STX1B-related fever-associated epilepsy models. (meyer2024characterizationsofa pages 9-12) - Zebrafish hyperthermia-induced seizure models highlighted as rapid screening tools for fever-triggered seizure mechanisms, with mechanistic intervention testing (e.g., TRPV4 and NMDA antagonists). (gyamfi2025voltagegatedsodiumchannel pages 14-16)

Expert opinion / analysis (evidence-based)

1. Syndrome definition has evolved: renaming away from “generalized” reflects recognition of focal seizures within the GEFS+ spectrum; this impacts clinical classification and gene-panel design. (li2024gabrg2mutationsin pages 1-2)
2. GEFS+ is best conceptualized as a spectrum rather than a single phenotype, spanning from FS/FS+ to DEE (e.g., Dravet), and is influenced by both rare variants and background genetic risk. (agathe2025polygenicriskscore pages 1-2)
3. Clinical implementation trend (2023–2024): expanding use of gene panels followed by WES/WGS in pediatric epilepsy and active development of gene-specific therapies in the SCN1A spectrum signal a near-term shift toward precision medicine in fever-triggered genetic epilepsies. (barcia2025geneticetiologieswith pages 2-4, NCT05419492 chunk 1)

Statistics and recent data points (explicitly retrieved)

• TNGS panel diagnostic yield in GEFS+: 16% (62 patients) in a 1000-patient pediatric epilepsy cohort. (barcia2025geneticetiologieswith pages 2-4)
• Cohort phenotype frequencies: FS 41% and FS+ 20% in a 201-person/31-family GEFS+ cohort summary. (li2024gabrg2mutationsin pages 6-7)
• Penetrance estimates: ~60% penetrance in GEFS+ pedigrees (with higher penetrance in some families; ~80% cited in a classic family analysis). (wallace1998febrileseizuresand pages 1-2, lerche2001generalizedepilepsywith pages 1-2)
• General pediatric febrile seizure frequency: ~3% in one classic genetics paper; 2–4% in another summary. (wallace1998febrileseizuresand pages 1-2, meyer2024characterizationsofa pages 9-12)

Direct abstract quotes (as required; from retrieved abstracts)

• Li et al., 2024 (Journal of Translational Medicine; Aug 2024; URL https://doi.org/10.1186/s12967-024-05387-1): “Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait.” (li2024gabrg2mutationsin pages 1-2)
• Barcia et al., 2025 (Epilepsia Open; May 2025; URL https://doi.org/10.1002/epi4.70057): “Patients with GEFS+ had a yield of 16%.” (barcia2025geneticetiologieswith pages 2-4)

Limitations of this report (evidence availability)

• PMID coverage: Several classic and review sources were retrieved with DOIs and full text but without explicit PMIDs in the extracted text segments; PubMed IDs are available for some gene–disease links via Open Targets, but a comprehensive PMID-mapped bibliography was not fully recoverable from the current corpus. (OpenTargets Search: Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+, wallace1998febrileseizuresand pages 1-2, li2024gabrg2mutationsin pages 1-2)
• ICD-10/ICD-11/MeSH identifiers were not retrieved and are therefore not reported. (escayg2001anovelscn1a pages 8-8)
• GEFS+-specific prevalence/incidence and SUDEP risk were not retrieved; only febrile-seizure general-population frequencies and familial penetrance/natural history statistics were available. (meyer2024characterizationsofa pages 9-12, wallace1998febrileseizuresand pages 1-2)

References

1. (OpenTargets Search: Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+): Open Targets Query (Genetic epilepsy with febrile seizures plus,Generalized epilepsy with febrile seizures plus,GEFS+, 32 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

2. (agathe2025polygenicriskscore pages 1-2): Jean-Madeleine De Sainte Agathe and Eric Leguern. Polygenic risk score to the rescue of monogenic diseases? the case of epilepsy. Jan 2025. URL: https://doi.org/10.1016/j.ebiom.2024.105505, doi:10.1016/j.ebiom.2024.105505. This article has 0 citations and is from a peer-reviewed journal.

3. (wallace2001neuronalsodiumchannelalpha1subunit pages 1-2): R. Wallace, R. Wallace, I. Scheffer, Scott A. Barnett, M. C. Richards, L. Dibbens, L. Dibbens, R. Desai, T. Lerman-Sagie, D. Lev, A. Mazarib, N. Brand, B. Ben-Zeev, I. Goikhman, Rita Singh, G. Kremmidiotis, G. Kremmidiotis, A. Gardner, G. Sutherland, G. Sutherland, A. George, J. Mulley, J. Mulley, and S. Berkovic. Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. American journal of human genetics, 68 4:859-65, Apr 2001. URL: https://doi.org/10.1086/319516, doi:10.1086/319516. This article has 519 citations and is from a highest quality peer-reviewed journal.

4. (escayg2001anovelscn1a pages 8-8): Andrew Escayg, Armin Heils, Bryan T. MacDonald, Karsten Haug, Thomas Sander, and Miriam H. Meisler. A novel scn1a mutation associated with generalized epilepsy with febrile seizures plus–and prevalence of variants in patients with epilepsy. American journal of human genetics, 68 4:866-73, Apr 2001. URL: https://doi.org/10.1086/319524, doi:10.1086/319524. This article has 411 citations and is from a highest quality peer-reviewed journal.

5. (li2024gabrg2mutationsin pages 1-2): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

6. (wallace1998febrileseizuresand pages 1-2): Robyn H. Wallace, Dao W. Wang, Rita Singh, Ingrid E. Scheffer, Alfred L. George, Hilary A. Phillips, Kathrin Saar, Andre Reis, Eric W. Johnson, Grant R. Sutherland, Samuel F. Berkovic, and John C. Mulley. Febrile seizures and generalized epilepsy associated with a mutation in the na+-channel ß1 subunit gene scn1b. Nature Genetics, 19:366-370, Aug 1998. URL: https://doi.org/10.1038/1252, doi:10.1038/1252. This article has 1474 citations and is from a highest quality peer-reviewed journal.

7. (gyamfi2025voltagegatedsodiumchannel pages 14-16): Angela Gyamfi, Priyadharshini Manikandan, William A. Cisneros, Theodore R. Cummins, and James A. Marrs. Voltage-gated sodium channel dysfunction in epilepsy: zebrafish models for therapeutics. Biomedicines, 13:2078, Aug 2025. URL: https://doi.org/10.3390/biomedicines13092078, doi:10.3390/biomedicines13092078. This article has 1 citations.

8. (li2024gabrg2mutationsin pages 6-7): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

9. (meyer2024characterizationsofa pages 9-12): Anjela Catherine Meyer. Characterizations of a heterozygous stx1b-knockout mouse model with fever associated epilepsy. Mar 2024. URL: https://doi.org/10.15496/publikation-92758, doi:10.15496/publikation-92758. This article has 0 citations.

10. (lerche2001generalizedepilepsywith pages 1-2): H. Lerche, Y. G. Weber, H. Baier, K. Jurkat–Rott, O. Kraus de Camargo, A. C. Ludolph, H. Bode, and F. Lehmann–Horn. Generalized epilepsy with febrile seizures plus. Neurology, 57:1191-1198, Oct 2001. URL: https://doi.org/10.1212/wnl.57.7.1191, doi:10.1212/wnl.57.7.1191. This article has 70 citations and is from a highest quality peer-reviewed journal.

11. (wallace1998febrileseizuresand pages 2-3): Robyn H. Wallace, Dao W. Wang, Rita Singh, Ingrid E. Scheffer, Alfred L. George, Hilary A. Phillips, Kathrin Saar, Andre Reis, Eric W. Johnson, Grant R. Sutherland, Samuel F. Berkovic, and John C. Mulley. Febrile seizures and generalized epilepsy associated with a mutation in the na+-channel ß1 subunit gene scn1b. Nature Genetics, 19:366-370, Aug 1998. URL: https://doi.org/10.1038/1252, doi:10.1038/1252. This article has 1474 citations and is from a highest quality peer-reviewed journal.

12. (escayg2001anovelscn1a pages 1-2): Andrew Escayg, Armin Heils, Bryan T. MacDonald, Karsten Haug, Thomas Sander, and Miriam H. Meisler. A novel scn1a mutation associated with generalized epilepsy with febrile seizures plus–and prevalence of variants in patients with epilepsy. American journal of human genetics, 68 4:866-73, Apr 2001. URL: https://doi.org/10.1086/319524, doi:10.1086/319524. This article has 411 citations and is from a highest quality peer-reviewed journal.

13. (li2024gabrg2mutationsin media a0660f7d): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

14. (li2024gabrg2mutationsin media 969b1bdb): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

15. (li2024gabrg2mutationsin media 78a53eaa): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

16. (li2024gabrg2mutationsin media 591accf4): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

17. (barcia2025geneticetiologieswith pages 2-4): Giulia Barcia, Nicole Chemaly, Stéphanie Gobin‐Limballe, Emma Losito, Mélodie Aubart, Eugénie Sarda, Zahra Assouline, Pauline Plante‐Bordeneuve, Marie Hully, Remi Barrois, Christine Barnerias, Doxa Sareidaki, Delphine Coste Zeitoun, Monika Eisermann, Cécile Fourrage, Sylvain Hanein, Marlène Rio, Nathalie Boddaert, Isabelle Desguerre, Anna Kaminska, Julie Steffann, and Rima Nabbout. Genetic etiologies with a large ngs panel in a monocentric cohort of 1000 patients with pediatric onset epilepsies. Epilepsia Open, 10:1065-1073, May 2025. URL: https://doi.org/10.1002/epi4.70057, doi:10.1002/epi4.70057. This article has 9 citations and is from a peer-reviewed journal.

18. (barcia2025geneticetiologieswith pages 1-2): Giulia Barcia, Nicole Chemaly, Stéphanie Gobin‐Limballe, Emma Losito, Mélodie Aubart, Eugénie Sarda, Zahra Assouline, Pauline Plante‐Bordeneuve, Marie Hully, Remi Barrois, Christine Barnerias, Doxa Sareidaki, Delphine Coste Zeitoun, Monika Eisermann, Cécile Fourrage, Sylvain Hanein, Marlène Rio, Nathalie Boddaert, Isabelle Desguerre, Anna Kaminska, Julie Steffann, and Rima Nabbout. Genetic etiologies with a large ngs panel in a monocentric cohort of 1000 patients with pediatric onset epilepsies. Epilepsia Open, 10:1065-1073, May 2025. URL: https://doi.org/10.1002/epi4.70057, doi:10.1002/epi4.70057. This article has 9 citations and is from a peer-reviewed journal.

19. (andjelkovic2024characterizationof13 pages 1-2): Marina Andjelkovic, Kristel Klaassen, Anita Skakic, Irena Marjanovic, Ruzica Kravljanac, Maja Djordjevic, Biljana Vucetic Tadic, Bozica Kecman, Sonja Pavlovic, and Maja Stojiljkovic. Characterization of 13 novel genetic variants in genes associated with epilepsy: implications for targeted therapeutic strategies. Molecular Diagnosis & Therapy, 28:645-663, Jul 2024. URL: https://doi.org/10.1007/s40291-024-00720-2, doi:10.1007/s40291-024-00720-2. This article has 12 citations and is from a peer-reviewed journal.

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21. (NCT05419492 chunk 2): A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome. Encoded Therapeutics. 2024. ClinicalTrials.gov Identifier: NCT05419492

22. (li2024gabrg2mutationsin pages 20-21): Xinxiao Li, Shengnan Guo, Yangyang Sun, Jiangwei Ding, Chao Chen, Yue-hui Wu, Peidong Li, Tao Sun, and Xinjun Wang. Gabrg2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics. Journal of Translational Medicine, Aug 2024. URL: https://doi.org/10.1186/s12967-024-05387-1, doi:10.1186/s12967-024-05387-1. This article has 11 citations and is from a peer-reviewed journal.

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