Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by treatment-resistant seizures beginning in infancy, developmental regression, and cognitive impairment. It is primarily caused by de novo loss-of-function mutations in SCN1A, encoding the Nav1.1 voltage-gated sodium channel.
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name: Dravet_syndrome
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-04-28T18:00:00Z'
description: Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by treatment-resistant seizures beginning in infancy, developmental regression, and cognitive impairment. It is primarily caused by de novo loss-of-function mutations in SCN1A, encoding the Nav1.1 voltage-gated sodium channel.
category: Genetic
disease_term:
preferred_term: Dravet syndrome
term:
id: MONDO:0100135
label: Dravet syndrome
mappings:
mondo_mappings:
- term:
id: MONDO:0100135
label: Dravet syndrome
mapping_predicate: skos:exactMatch
mapping_source: Orphanet
mapping_justification: Orphanet ORPHA:33069 lists MONDO:0011794 as an exact cross-reference; MONDO:0100135 is the current preferred MONDO identifier for Dravet syndrome.
consistency:
- reference: ORPHA:33069
consistent: CONSISTENT
notes: "ORPHA cross-reference row: MONDO:0011794 | Exact"
external_assertions:
- name: Orphanet Dravet syndrome record
source: Orphanet
assertion_type: structured_disease_record
external_id: ORPHA:33069
url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=33069
description: >
Orphanet identifies Dravet syndrome as ORPHA:33069 and provides
exact cross-references including MONDO:0011794 and OMIM:607208.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "MONDO:0011794 | Exact"
explanation: Orphanet's cross-reference table maps ORPHA:33069 exactly to the MONDO term for Dravet syndrome.
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "OMIM:607208 | Exact"
explanation: Orphanet also provides an exact OMIM cross-reference for Dravet syndrome.
parents:
- Epileptic Encephalopathy
- Neurologic Disorder
inheritance:
- name: Autosomal dominant inheritance
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
description: >
Orphanet classifies Dravet syndrome as autosomal dominant,
consistent with de novo heterozygous loss-of-function mutations in SCN1A.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "Autosomal dominant"
explanation: Orphanet directly lists autosomal dominant inheritance for ORPHA:33069.
prevalence:
- population: Europe
percentage: "1-9 / 100 000"
notes: >
Orphanet prevalence at birth class for Dravet syndrome. Population-based
studies estimate incidence of 1:40,900 UK births (PMID:22719002),
1:33,000 Swedish births (PMID:25772213), and SCN1A-specific incidence of
1:12,200 Scottish births (PMID:31302675).
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "1-9 / 100 000 | Europe | Prevalence at birth | PMID:22719002,PMID:25772213,PMID:31302675"
explanation: Orphanet reports the European prevalence-at-birth class for Dravet syndrome based on three population-based studies.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The incidence of mutation-positive Dravet syndrome is at least 1:40 900 UK births."
explanation: UK population-based cohort establishing incidence of SCN1A mutation-positive Dravet syndrome.
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The estimated incidence was one in 33 000 live births (95% CI 1:20 400-1:56 200)"
explanation: Swedish population-based study confirming Dravet syndrome incidence.
- reference: PMID:31302675
reference_title: "Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93-12.6)"
explanation: Scottish prospective cohort providing SCN1A-specific epilepsy incidence.
progression:
- phase: Onset
age_range: Infancy to Neonatal
notes: >
Orphanet lists onset as Infancy and Neonatal. Seizures typically begin
between 3 and 12 months of age, often triggered by fever.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "Age of onset: Infancy"
explanation: Orphanet's natural-history section classifies Dravet syndrome onset as infantile.
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the median age at seizure onset was 6 months (range 0-12mo)"
explanation: Swedish cohort confirms median seizure onset at 6 months.
pathophysiology:
- name: SCN1A Gene Mutation
description: Heterozygous loss-of-function mutations in SCN1A cause reduced Nav1.1 sodium channel function, primarily affecting GABAergic inhibitory interneurons, particularly parvalbumin-positive fast-spiking interneurons.
cell_types:
- preferred_term: inhibitory interneuron
term:
id: CL:0000498
label: inhibitory interneuron
biological_processes:
- preferred_term: neuronal action potential
term:
id: GO:0019228
label: neuronal action potential
molecular_functions:
- preferred_term: voltage-gated sodium channel activity
term:
id: GO:0005248
label: voltage-gated sodium channel activity
locations:
- preferred_term: cerebral cortex
term:
id: UBERON:0000956
label: cerebral cortex
- preferred_term: Ammon's horn
term:
id: UBERON:0001954
label: Ammon's horn
evidence:
- reference: PMID:21463282
reference_title: "Insights into pathophysiology and therapy from a mouse model of Dravet syndrome."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Loss-of-function in Na(v) 1.1 channels results in severely impaired sodium current and action potential firing in hippocampal γ-aminobutyric acid (GABA)ergic interneurons without detectable changes in excitatory pyramidal neurons.
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN1A | sodium voltage-gated channel alpha subunit 1 | hgnc:10585 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table confirms SCN1A as a disease-causing gene for Dravet syndrome.
- name: Neuronal Hyperexcitability
description: Reduced inhibitory interneuron function leads to excitatory-inhibitory imbalance and network hyperexcitability across cortico-hippocampal and thalamocortical circuits.
cell_types:
- preferred_term: inhibitory interneuron
term:
id: CL:0000498
label: inhibitory interneuron
biological_processes:
- preferred_term: synaptic transmission, GABAergic
term:
id: GO:0051932
label: synaptic transmission, GABAergic
locations:
- preferred_term: cerebral cortex
term:
id: UBERON:0000956
label: cerebral cortex
- preferred_term: Ammon's horn
term:
id: UBERON:0001954
label: Ammon's horn
- preferred_term: dorsal plus ventral thalamus
term:
id: UBERON:0001897
label: dorsal plus ventral thalamus
evidence:
- reference: PMID:21463282
reference_title: "Insights into pathophysiology and therapy from a mouse model of Dravet syndrome."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: The resulting imbalance between excitation and inhibition likely contributes to hyperexcitability and seizures.
- name: Astrocyte Dysregulation
description: Aberrant astrocyte calcium signaling and gliotransmission may exacerbate network hyperexcitability and seizure susceptibility.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
locations:
- preferred_term: cerebral cortex
term:
id: UBERON:0000956
label: cerebral cortex
- preferred_term: Ammon's horn
term:
id: UBERON:0001954
label: Ammon's horn
phenotypes:
- category: Neurologic
name: Seizures
description: Treatment-resistant seizures beginning in the first year of life, often triggered by fever, with progression to multiple seizure types.
frequency: VERY_FREQUENT
diagnostic: true
notes: Include prolonged febrile seizures and various types of epilepsy as the condition progresses.
evidence:
- reference: PMID:21463282
reference_title: "Insights into pathophysiology and therapy from a mouse model of Dravet syndrome."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: a devastating infantile-onset epilepsy with ataxia, cognitive dysfunction, and febrile and afebrile seizures resistant to current medications.
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007359 | Focal-onset seizure | Very frequent (99-80%)"
explanation: Orphanet's curated HPO table classifies focal-onset seizures as very frequent in Dravet syndrome, corroborating the high seizure burden.
phenotype_term:
preferred_term: Seizures
term:
id: HP:0001250
label: Seizure
- category: Neurologic
name: Focal-onset Seizure
description: >
Focal-onset seizures are a very frequent seizure type in Dravet syndrome,
classified by Orphanet among the most common manifestations.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Focal-onset seizure
term:
id: HP:0007359
label: Focal-onset seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007359 | Focal-onset seizure | Very frequent (99-80%)"
explanation: Orphanet's curated HPO table classifies focal-onset seizures as very frequent in Dravet syndrome.
- category: Neurologic
name: Febrile Seizures
description: Seizures triggered by fever, typically the presenting feature in infancy between 3 months and 6 years. Often prolonged hemiclonic seizures or status epilepticus.
frequency: FREQUENT
diagnostic: true
notes: Characteristic presenting feature in early infancy, often prompts genetic evaluation for Dravet syndrome.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002373 | Febrile seizure (within the age range of 3 months to 6 years) | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies febrile seizures as frequent in Dravet syndrome.
phenotype_term:
preferred_term: Febrile seizure (within the age range of 3 months to 6 years)
term:
id: HP:0002373
label: Febrile seizure (within the age range of 3 months to 6 years)
- category: Neurologic
name: Complex Febrile Seizure
description: >
Prolonged or focal febrile seizures, frequently the presenting seizure
type in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Complex febrile seizure
term:
id: HP:0011172
label: Complex febrile seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011172 | Complex febrile seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies complex febrile seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Focal Hemiclonic Seizure
description: >
Hemiclonic seizures are a frequent and characteristic seizure type in
Dravet syndrome, often occurring during the initial febrile presentation.
frequency: FREQUENT
phenotype_term:
preferred_term: Focal hemiclonic seizure
term:
id: HP:0006813
label: Focal hemiclonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0006813 | Focal hemiclonic seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies focal hemiclonic seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Generalized Myoclonic Seizure
description: >
Myoclonic seizures are a frequent seizure type in Dravet syndrome,
consistent with its historical designation as severe myoclonic epilepsy
of infancy (SMEI).
frequency: FREQUENT
phenotype_term:
preferred_term: Generalized myoclonic seizure
term:
id: HP:0002123
label: Generalized myoclonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002123 | Generalized myoclonic seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies generalized myoclonic seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Photosensitive Myoclonic Seizures
description: >
Seizures triggered by photic stimulation, a frequent feature in
Dravet syndrome reflecting photosensitivity.
frequency: FREQUENT
phenotype_term:
preferred_term: Photosensitive myoclonic seizures
term:
id: HP:0001327
label: Photosensitive myoclonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0001327 | Photomyoclonic seizures | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies photomyoclonic seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Photosensitive Tonic-Clonic Seizures
description: >
Tonic-clonic seizures triggered by photosensitivity, a frequent
manifestation in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Photosensitive tonic-clonic seizures
term:
id: HP:0007207
label: Photosensitive tonic-clonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007207 | Photosensitive tonic-clonic seizures | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies photosensitive tonic-clonic seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Focal Aware Seizure
description: >
Focal seizures with preserved awareness, a frequent seizure type in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Focal aware seizure
term:
id: HP:0002349
label: Focal aware seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002349 | Focal aware seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies focal aware seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Focal Impaired Awareness Seizure
description: >
Focal seizures with impaired awareness, a frequent seizure type in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Focal impaired awareness seizure
term:
id: HP:0002384
label: Focal impaired awareness seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002384 | Focal impaired awareness seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies focal impaired awareness seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Atypical Absence Seizure
description: >
Atypical absence seizures are a frequent seizure type in the Dravet
syndrome spectrum.
frequency: FREQUENT
phenotype_term:
preferred_term: Atypical absence seizure
term:
id: HP:0007270
label: Atypical absence seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007270 | Atypical absence seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies atypical absence seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Generalized Clonic Seizure
description: >
Generalized clonic seizures are among the frequent seizure types in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Generalized clonic seizure
term:
id: HP:0011169
label: Generalized clonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011169 | Generalized clonic seizure | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies generalized clonic seizures as frequent in Dravet syndrome.
- category: Neurologic
name: Epilepsia Partialis Continua
description: >
Continuous focal seizure activity, listed as a frequent manifestation
in Dravet syndrome by Orphanet.
frequency: FREQUENT
phenotype_term:
preferred_term: Epilepsia partialis continua
term:
id: HP:0012847
label: Epilepsia partialis continua
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0012847 | Epilepsia partialis continua | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies epilepsia partialis continua as frequent in Dravet syndrome.
- category: Neurologic
name: Status Epilepticus Without Prominent Motor Symptoms
description: >
Non-convulsive status epilepticus, an occasional manifestation in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Status epilepticus without prominent motor symptoms
term:
id: HP:0031475
label: Status epilepticus without prominent motor symptoms
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0031475 | Status epilepticus without prominent motor symptoms | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies non-convulsive status epilepticus as occasional in Dravet syndrome.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "status epilepticus (odds ratio = 3.1; confidence interval = 1.5-6.3; P = 0.003)"
explanation: Brunklaus et al. identify status epilepticus as a significant prognostic predictor of worse developmental outcome.
- category: Neurologic
name: Generalized Tonic Seizure
description: >
Generalized tonic seizures are a very rare seizure type in Dravet syndrome.
frequency: VERY_RARE
phenotype_term:
preferred_term: Generalized tonic seizure
term:
id: HP:0010818
label: Generalized tonic seizure
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0010818 | Generalized tonic seizure | Very rare (<4-1%)"
explanation: Orphanet's curated HPO table classifies generalized tonic seizures as very rare in Dravet syndrome.
- category: Neurologic
name: Multifocal Epileptiform Discharges
description: >
EEG finding of multifocal epileptiform discharges, frequently seen in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Multifocal epileptiform discharges
term:
id: HP:0010841
label: Multifocal epileptiform discharges
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0010841 | Multifocal epileptiform discharges | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies multifocal epileptiform discharges as frequent in Dravet syndrome.
- category: Neurologic
name: Interictal Epileptiform Activity
description: >
EEG epileptiform activity between seizures, a frequent finding in
Dravet syndrome. Early interictal abnormalities are prognostically significant.
frequency: FREQUENT
phenotype_term:
preferred_term: Interictal epileptiform activity
term:
id: HP:0011182
label: Interictal epileptiform activity
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011182 | Interictal epileptiform activity | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies interictal epileptiform activity as frequent in Dravet syndrome.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "interictal electroencephalography abnormalities in the first year of life (odds ratio = 5.7; confidence interval = 1.9-16.8; P = 0.002)"
explanation: UK cohort identifies interictal EEG abnormalities in the first year as a strong predictor of worse developmental outcome.
- category: Neurologic
name: EEG with Focal Epileptiform Discharges
description: >
Focal epileptiform discharges on EEG, an occasional finding in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: EEG with focal epileptiform discharges
term:
id: HP:0011185
label: EEG with focal epileptiform discharges
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011185 | EEG with focal epileptiform discharges | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies focal EEG epileptiform discharges as occasional in Dravet syndrome.
- category: Neurologic
name: EEG with Generalized Epileptiform Discharges
description: >
Generalized epileptiform discharges on EEG, an occasional finding in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: EEG with generalized epileptiform discharges
term:
id: HP:0011198
label: EEG with generalized epileptiform discharges
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011198 | EEG with generalized epileptiform discharges | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies generalized EEG epileptiform discharges as occasional in Dravet syndrome.
- category: Developmental
name: Developmental Regression
description: >
Progressive developmental regression typically beginning after
seizure onset, affecting motor, language, and social skills.
Classified as very frequent by Orphanet.
frequency: VERY_FREQUENT
evidence:
- reference: PMID:21463282
reference_title: "Insights into pathophysiology and therapy from a mouse model of Dravet syndrome."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: a devastating infantile-onset epilepsy with ataxia, cognitive dysfunction, and febrile and afebrile seizures resistant to current medications.
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002376 | Developmental regression | Very frequent (99-80%)"
explanation: Orphanet's curated HPO table classifies developmental regression as very frequent in Dravet syndrome.
phenotype_term:
preferred_term: Developmental regression
term:
id: HP:0002376
label: Developmental regression
- category: Cognitive
name: Cognitive Impairment
description: Cognitive impairment ranging from mild to severe, often progressive in nature.
frequency: FREQUENT
notes: Ranges from mild to severe.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100543 | Cognitive impairment | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies cognitive impairment as frequent in Dravet syndrome.
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Intellectual disability was diagnosed in 28 (67%) children"
explanation: Swedish population-based study found intellectual disability in 67% of children with Dravet syndrome.
phenotype_term:
preferred_term: Cognitive impairment
term:
id: HP:0100543
label: Cognitive impairment
- category: Neurologic
name: Progressive Gait Ataxia
description: >
Progressive gait ataxia is a very frequent manifestation in Dravet
syndrome, affecting coordination and balance with worsening over time.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007240 | Progressive gait ataxia | Very frequent (99-80%)"
explanation: Orphanet's curated HPO table classifies progressive gait ataxia as very frequent in Dravet syndrome.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "motor disorder (odds ratio = 3.3; confidence interval = 1.7-6.4; P < 0.001)"
explanation: UK cohort identifies motor disorder as a strong predictor of worse developmental outcome, consistent with prominent gait ataxia.
phenotype_term:
preferred_term: Progressive gait ataxia
term:
id: HP:0007240
label: Progressive gait ataxia
- category: Behavioral
name: Autistic Behavior
description: Autism spectrum features including impaired social interaction, communication difficulties, and restricted repetitive behaviors.
frequency: FREQUENT
notes: Behavioral and autism-like traits frequently observed and may relate to disrupted circuit development.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000729 | Autistic behavior | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies autistic behavior as frequent in Dravet syndrome.
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "18 out of 30 patients investigated had autism spectrum disorder"
explanation: Swedish population-based study found autism spectrum disorder in 60% of investigated Dravet patients.
phenotype_term:
preferred_term: Autistic behavior
term:
id: HP:0000729
label: Autistic behavior
- category: Behavioral
name: Anxiety
description: >
Anxiety is a frequent behavioral feature in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Anxiety
term:
id: HP:0000739
label: Anxiety
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000739 | Anxiety | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies anxiety as frequent in Dravet syndrome.
- category: Behavioral
name: Obsessive-Compulsive Trait
description: >
Obsessive-compulsive behavioral traits are a frequent feature in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Obsessive-compulsive trait
term:
id: HP:0008770
label: Obsessive-compulsive trait
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0008770 | Obsessive-compulsive trait | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies obsessive-compulsive traits as frequent in Dravet syndrome.
- category: Behavioral
name: Short Attention Span
description: >
Attention deficits and short attention span, an occasional behavioral
feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Short attention span
term:
id: HP:0000736
label: Short attention span
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000736 | Short attention span | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies short attention span as occasional in Dravet syndrome.
- category: Behavioral
name: Impulsivity
description: >
Impulsive behavior, an occasional behavioral feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Impulsivity
term:
id: HP:0100710
label: Impulsivity
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100710 | Impulsivity | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies impulsivity as occasional in Dravet syndrome.
- category: Neurologic
name: Myoclonus
description: >
Non-epileptic myoclonus is a frequent motor feature in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Myoclonus
term:
id: HP:0001336
label: Myoclonus
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0001336 | Myoclonus | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies myoclonus as frequent in Dravet syndrome.
- category: Neurologic
name: Parkinsonism
description: >
Parkinsonian features including rigidity, bradykinesia, and cogwheel
rigidity, emerging as frequent manifestations particularly in older
patients with Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Parkinsonism
term:
id: HP:0001300
label: Parkinsonism
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0001300 | Parkinsonism | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies parkinsonism as frequent in Dravet syndrome.
- category: Neurologic
name: Rigidity
description: >
Muscular rigidity is a frequent motor feature in Dravet syndrome,
part of the parkinsonian phenotype spectrum.
frequency: FREQUENT
phenotype_term:
preferred_term: Rigidity
term:
id: HP:0002063
label: Rigidity
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002063 | Rigidity | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies rigidity as frequent in Dravet syndrome.
- category: Neurologic
name: Bradykinesia
description: >
Slowness of movement, a frequent feature of the parkinsonian
phenotype in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Bradykinesia
term:
id: HP:0002067
label: Bradykinesia
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002067 | Bradykinesia | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies bradykinesia as frequent in Dravet syndrome.
- category: Neurologic
name: Cogwheel Rigidity
description: >
Cogwheel-type rigidity, a frequent parkinsonian feature in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Cogwheel rigidity
term:
id: HP:0002396
label: Cogwheel rigidity
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002396 | Cogwheel rigidity | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies cogwheel rigidity as frequent in Dravet syndrome.
- category: Neurologic
name: Action Tremor
description: >
Tremor during voluntary movement, an occasional motor feature in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Action tremor
term:
id: HP:0002345
label: Action tremor
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002345 | Action tremor | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies action tremor as occasional in Dravet syndrome.
- category: Neurologic
name: Facial Tics
description: >
Facial tics are a frequent motor feature in Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Facial tics
term:
id: HP:0011468
label: Facial tics
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0011468 | Facial tics | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies facial tics as frequent in Dravet syndrome.
- category: Neurologic
name: Incoordination
description: >
General motor incoordination, an occasional feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Incoordination
term:
id: HP:0002311
label: Incoordination
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002311 | Incoordination | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies incoordination as occasional in Dravet syndrome.
- category: Neurologic
name: Poor Fine Motor Coordination
description: >
Impaired fine motor skills, an occasional feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Poor fine motor coordination
term:
id: HP:0007010
label: Poor fine motor coordination
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0007010 | Poor fine motor coordination | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies poor fine motor coordination as occasional in Dravet syndrome.
- category: Neurologic
name: Drooling
description: >
Drooling (sialorrhea), an occasional feature in Dravet syndrome
reflecting oropharyngeal motor dysfunction.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Drooling
term:
id: HP:0002307
label: Drooling
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002307 | Drooling | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies drooling as occasional in Dravet syndrome.
- category: Neurologic
name: Floppy Infant
description: >
Infantile hypotonia, an occasional early feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Floppy infant
term:
id: HP:0008947
label: Floppy infant
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0008947 | Floppy infant | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies infantile hypotonia as occasional in Dravet syndrome.
- category: Neuroimaging
name: Global Brain Atrophy
description: >
Non-specific brain atrophy on neuroimaging, an occasional finding in
Dravet syndrome.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002283 | Global brain atrophy | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies global brain atrophy as occasional in Dravet syndrome.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Abnormal magnetic resonance imaging was documented in 11% of cases, principally with findings of non-specific brain atrophy or hippocampal changes."
explanation: UK cohort found brain atrophy or hippocampal changes in 11% of Dravet cases.
phenotype_term:
preferred_term: Global brain atrophy
term:
id: HP:0002283
label: Global brain atrophy
- category: Neuroimaging
name: Dysgenesis of the Hippocampus
description: >
Hippocampal structural abnormalities, an occasional neuroimaging
finding in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Dysgenesis of the hippocampus
term:
id: HP:0025101
label: Dysgenesis of the hippocampus
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0025101 | Dysgenesis of the hippocampus | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies hippocampal dysgenesis as occasional in Dravet syndrome.
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "principally with findings of non-specific brain atrophy or hippocampal changes"
explanation: UK cohort found hippocampal changes among the neuroimaging abnormalities in Dravet syndrome.
- category: Musculoskeletal
name: Limited Neck Range of Motion
description: >
Restricted neck mobility, a frequent musculoskeletal feature in
Dravet syndrome.
frequency: FREQUENT
phenotype_term:
preferred_term: Limited neck range of motion
term:
id: HP:0000466
label: Limited neck range of motion
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000466 | Limited neck range of motion | Frequent (79-30%)"
explanation: Orphanet's curated HPO table classifies limited neck range of motion as frequent in Dravet syndrome.
- category: Musculoskeletal
name: Pes Planus
description: >
Flat feet, an occasional musculoskeletal feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Pes planus
term:
id: HP:0001763
label: Pes planus
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0001763 | Pes planus | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies pes planus as occasional in Dravet syndrome.
- category: Musculoskeletal
name: Pes Valgus
description: >
Valgus foot deformity, an occasional musculoskeletal feature in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Pes valgus
term:
id: HP:0008081
label: Pes valgus
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0008081 | Pes valgus | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies pes valgus as occasional in Dravet syndrome.
- category: Musculoskeletal
name: Limited Knee Extension
description: >
Restricted knee extension, an occasional musculoskeletal feature in
Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Limited knee extension
term:
id: HP:0003066
label: Limited knee extension
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0003066 | Limited knee extension | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies limited knee extension as occasional in Dravet syndrome.
- category: Musculoskeletal
name: Tibial Torsion
description: >
Tibial torsion, an occasional orthopedic feature in Dravet syndrome.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Tibial torsion
term:
id: HP:0100694
label: Tibial torsion
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100694 | Tibial torsion | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies tibial torsion as occasional in Dravet syndrome.
- category: Other
name: Pallor
description: >
Pallor is an occasional feature in Dravet syndrome, which may occur
during ictal or postictal periods.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Pallor
term:
id: HP:0000980
label: Pallor
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000980 | Pallor | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies pallor as occasional in Dravet syndrome.
- category: Other
name: Cyanotic Episode
description: >
Episodes of cyanosis, an occasional feature in Dravet syndrome
potentially related to ictal autonomic dysfunction.
frequency: OCCASIONAL
phenotype_term:
preferred_term: Cyanotic episode
term:
id: HP:0200048
label: Cyanotic episode
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0200048 | Cyanotic episode | Occasional (29-5%)"
explanation: Orphanet's curated HPO table classifies cyanotic episodes as occasional in Dravet syndrome.
- category: Respiratory
name: Respiratory Failure
description: Postictal respiratory compromise and sleep-associated breathing abnormalities contributing to SUDEP risk.
frequency: OCCASIONAL
notes: Postictal ventilatory dysfunction can occur, particularly during sleep.
phenotype_term:
preferred_term: Respiratory failure
term:
id: HP:0002878
label: Respiratory failure
- category: Mortality
name: Sudden Unexpected Death in Epilepsy
description: Markedly elevated risk of sudden unexpected death in epilepsy (SUDEP), accounting for up to 50% of deaths in Dravet syndrome. Linked to seizure burden, postictal cardiorespiratory dysfunction, and potential cardiac susceptibility.
frequency: OCCASIONAL
notes: High premature mortality with SUDEP as leading cause. Risk peaks at ages 1-3 years and around 18 years.
phenotype_term:
preferred_term: Sudden unexpected death in epilepsy
term:
id: HP:0033258
label: Sudden unexpected death in epilepsy
genetic:
- name: SCN1A
association: Pathogenic Mutations
presence: Positive
notes: De novo loss-of-function mutations found in approximately 70-80% of Dravet syndrome patients. Primary causal gene encoding Nav1.1 voltage-gated sodium channel.
evidence:
- reference: PMID:21463282
reference_title: "Insights into pathophysiology and therapy from a mouse model of Dravet syndrome."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Complete loss of function in the Na(v) 1.1 channel encoded by the SCN1A gene is associated with severe myoclonic epilepsy in infancy (SMEI)
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN1A | sodium voltage-gated channel alpha subunit 1 | hgnc:10585 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table confirms SCN1A as a disease-causing gene for Dravet syndrome.
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A mutation in the SCN1A gene was found in 37 patients (88%)"
explanation: Swedish population-based study found SCN1A mutations in 88% of Dravet patients.
- reference: CGGV:assertion_60334a15-c73e-42ce-b7d2-4796c2affde4-2019-08-20T160000.000Z
reference_title: "SCN1A / Dravet syndrome (Definitive)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN1A | HGNC:10585 | Dravet syndrome | MONDO:0100135 | AD | Definitive"
explanation: ClinGen classifies the SCN1A-Dravet syndrome gene-disease relationship as definitive with autosomal dominant inheritance.
- name: SCN1B
association: Rare Pathogenic Mutations
notes: Encodes beta-1 subunit of voltage-gated sodium channels. Rare variants associated with Dravet syndrome phenotype.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN1B | sodium voltage-gated channel beta subunit 1 | hgnc:10586 | Disease-causing germline mutation(s) (loss of function) in"
explanation: Orphanet gene table confirms SCN1B loss-of-function mutations as disease-causing in Dravet syndrome.
- name: SCN2A
association: Rare Pathogenic Mutations
notes: Encodes Nav1.2 sodium channel alpha subunit. Rare variants associated with Dravet syndrome phenotype.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN2A | sodium voltage-gated channel alpha subunit 2 | hgnc:10588 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table lists SCN2A as a disease-causing gene for Dravet syndrome.
- name: SCN9A
association: Candidate Gene
notes: Encodes Nav1.7 sodium channel. Candidate gene tested in atypical cases.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "SCN9A | sodium voltage-gated channel alpha subunit 9 | hgnc:10597 | Candidate gene tested in"
explanation: Orphanet gene table lists SCN9A as a candidate gene tested in Dravet syndrome.
- name: GABRA1
association: Rare Pathogenic Mutations
notes: Encodes GABA-A receptor alpha-1 subunit. Rare variants can cause Dravet-like epileptic encephalopathy.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "GABRA1 | gamma-aminobutyric acid type A receptor subunit alpha1 | hgnc:4075 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table confirms GABRA1 as a disease-causing gene for Dravet syndrome.
- name: GABRG2
association: Rare Pathogenic Mutations
notes: Encodes GABA-A receptor gamma-2 subunit. Variants associated with epileptic encephalopathy phenotypes overlapping with Dravet syndrome.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "GABRG2 | gamma-aminobutyric acid type A receptor subunit gamma2 | hgnc:4087 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table confirms GABRG2 as a disease-causing gene for Dravet syndrome.
- name: PCDH19
association: Rare Pathogenic Mutations
notes: Encodes protocadherin 19. Rare mutations associated with epileptic encephalopathy overlapping with Dravet syndrome, particularly in females.
evidence:
- reference: ORPHA:33069
reference_title: "Dravet syndrome (Orphanet structured-database record)"
supports: SUPPORT
evidence_source: OTHER
snippet: "PCDH19 | protocadherin 19 | hgnc:14270 | Disease-causing germline mutation(s) in"
explanation: Orphanet gene table lists PCDH19 as a disease-causing gene for Dravet syndrome.
- name: STXBP1
association: Rare Pathogenic Mutations
notes: Encodes syntaxin-binding protein 1. Mutations cause early infantile epileptic encephalopathy with phenotypic overlap.
- name: HCN1
association: Rare Associated Variants
notes: Encodes hyperpolarization-activated cyclic nucleotide-gated channel 1. Variants reported in early infantile epileptic encephalopathy.
- name: CHD2
association: Modifier Gene
notes: Encodes chromodomain helicase DNA-binding protein 2. Variants may modify disease severity and phenotype in Dravet syndrome.
- name: DEPDC5
association: Modifier Gene
notes: Encodes DEP domain-containing protein 5. Polygenic modifier that may influence disease expressivity and severity.
diagnosis:
- name: Genetic Testing for SCN1A Mutations
presence: Positive in affected individuals
treatments:
- name: Antiepileptic Medications
description: Includes clobazam, stiripentol, and valproate as first-line agents. Sodium channel blockers should be avoided as they may worsen seizures.
notes: Standard treatment includes clobazam, stiripentol, and valproate.
evidence:
- reference: PMID:22719002
reference_title: "Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Sodium valproate, benzodiazepines and topiramate were reported as being the most helpful medications at the time of referral. Aggravation of seizures was reported for carbamazepine and lamotrigine."
explanation: UK cohort confirms first-line medications and identifies sodium channel blockers that worsen seizures.
treatment_term:
preferred_term: antiepileptic drug therapy
term:
id: MAXO:0000167
label: anticonvulsant agent therapy
- name: Ketogenic Diet
description: High-fat, low-carbohydrate diet that can provide significant seizure reduction in some patients.
notes: Has shown efficacy in reducing seizure frequency in Dravet syndrome patients.
treatment_term:
preferred_term: dietary intervention
term:
id: MAXO:0000088
label: dietary intervention
- name: Supportive Therapies
description: Therapies such as physical, occupational, and speech therapy to address developmental delays and cognitive impairment.
notes: Comprehensive care includes developmental support and therapeutic interventions.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
- name: Vagus Nerve Stimulation (VNS)
description: Implanted device that may help reduce seizure frequency in drug-resistant cases.
notes: May be considered for patients with drug-resistant seizures.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Antisense Oligonucleotide Therapy (STK-001/Zorevunersen)
description: Investigational antisense oligonucleotide designed to upregulate productive SCN1A transcripts and restore Nav1.1 expression in inhibitory neurons. Preclinical studies show seizure reduction and SUDEP prevention. Early clinical data report good tolerability with reduced seizure frequency in treated individuals.
notes: Disease-modifying gene-targeted therapy in early clinical development. Represents precision approach to address underlying SCN1A haploinsufficiency.
treatment_term:
preferred_term: gene therapy
term:
id: MAXO:0001001
label: gene therapy
- name: AAV Gene Therapy (ETX101)
description: Investigational AAV9-based viral vector gene therapy designed to increase SCN1A expression through transcriptional activation in inhibitory neurons. Preclinical models demonstrate seizure reduction and improved survival.
notes: Disease-modifying gene therapy approaching clinical testing. Targets interneuron-specific SCN1A restoration.
treatment_term:
preferred_term: gene therapy
term:
id: MAXO:0001001
label: gene therapy
- name: Cannabidiol
description: Pharmaceutical-grade cannabidiol approved as add-on therapy for reducing convulsive seizure frequency in Dravet syndrome.
notes: Approved therapy with demonstrated efficacy in randomized controlled trials.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: cannabidiol
term:
id: CHEBI:69478
label: cannabidiol
- name: Fenfluramine
description: Approved add-on therapy for convulsive seizures in Dravet syndrome, with serotonergic mechanism of action.
notes: Effective therapy approved based on randomized controlled trial data.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: fenfluramine
term:
id: CHEBI:5000
label: fenfluramine
- name: Stiripentol
description: Approved antiepileptic drug used in combination with clobazam and valproate for convulsive seizures in Dravet syndrome.
notes: Part of standard first-line combination therapy.
evidence:
- reference: PMID:25772213
reference_title: "Dravet syndrome in Sweden: a population-based study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Stiripentol, as an add-on medication, was used in 18 patients. Among these patients, seven were seizure free, six had >50% seizure reduction, and five <50% seizure reduction."
explanation: Swedish cohort provides real-world efficacy data for stiripentol add-on therapy.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: stiripentol
term:
id: NCIT:C152433
label: Stiripentol
environmental:
- name: Fever
effect: Triggers Seizures
notes: Management of fever is crucial to minimize seizure risk.
- name: Excessive Heat and Overexertion
effect: Exacerbates Symptoms
notes: Can trigger or worsen seizures.
notes: Early diagnosis and a comprehensive treatment plan are essential to managing Dravet syndrome and improving quality of life.
classifications:
harrisons_chapter:
- classification_value: nervous system disorder
- classification_value: epilepsy
- classification_value: hereditary disease
references:
- reference: DOI:10.1007/s10309-025-00785-x
title: More than epilepsy—a parent-initiated collaborative analysis of the research landscape and research needs in Dravet syndrome
findings: []
- reference: DOI:10.1038/s41398-025-03304-8
title: Spotlight on mechanism of sudden unexpected death in epilepsy in Dravet syndrome
findings: []
- reference: DOI:10.3389/fnins.2025.1634718
title: 'Dravet syndrome: novel insights into SCN1A-mediated epileptic neurodevelopmental disorders within the molecular diagnostic-therapeutic framework'
findings: []
- reference: DOI:10.3390/jcm12072532
title: Epilepsy in Dravet Syndrome—Current and Future Therapeutic Opportunities
findings: []
Pathophysiology description Dravet syndrome (DS) is a developmental and epileptic encephalopathy most commonly caused by heterozygous loss-of-function variants in SCN1A encoding the Nav1.1 voltage‑gated sodium channel alpha subunit, producing inhibitory interneuron hypoexcitability, network disinhibition, and pharmacoresistant seizures that begin in infancy and are often fever‑triggered (febrile hemiclonic/status) (shao2025spotlightonmechanism pages 1-2, gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3). Reduced Nav1.1‑dependent sodium currents are especially prominent in parvalbumin‑positive (PV+) fast‑spiking GABAergic interneurons, disturbing excitatory/inhibitory balance across cortico‑hippocampal and thalamocortical circuits and contributing to cognitive, behavioral, sleep, and gait/motor comorbidities (shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22, konrad2025morethanepilepsy—a pages 2-3). Non‑neuronal mechanisms further modify disease: aberrant astrocyte Ca2+ signaling and metabolic/mitochondrial vulnerabilities are reported to exacerbate network hyperexcitability and phenotype severity; polygenic modifiers (e.g., DEPDC5, CHD2) may also influence expressivity (zhang2025dravetsyndromenovel pages 1-2, zhang2025dravetsyndromenovel pages 21-22). DS carries high premature mortality; SUDEP risk is markedly elevated and mechanistically linked to seizure burden, sleep‑associated events, and postictal cardiorespiratory dysfunction, with potential cardiac susceptibility in some cases (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 1-2, konrad2025morethanepilepsy—a pages 2-3).
Direct quotes supporting key statements - “The dominant genetic cause (70–80% of cases) is de novo heterozygous loss‑of‑function mutations in SCN1A, encoding the Nav1.1 α‑subunit” (Translational Psychiatry, Mar 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 1-2). - “SCN1A mutations disrupt Nav1.1… in GABAergic interneurons… impairing inhibitory synaptic transmission and disrupting brainwide excitatory–inhibitory balance” (Frontiers in Neuroscience, Jul 2025; https://doi.org/10.3389/fnins.2025.1634718) (zhang2025dravetsyndromenovel pages 1-2). - “Preclinical Scn1a‑ASO studies reduced seizures and SUDEP in mice, and early clinical data report STK‑001 was well tolerated with 70.6% of treated individuals showing decreased seizure frequency” (Translational Psychiatry, Mar 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 11-12). - “SUDEP… accounts for up to 50% of deaths in DS… mechanisms include cardiac arrhythmia… seizure burden… and postictal ventilatory dysfunction” (Clinical Epileptology, Nov 2025; https://doi.org/10.1007/s10309-025-00785-x) (konrad2025morethanepilepsy—a pages 2-3).
Affected cellular processes: impaired interneuron firing, reduced inhibitory tone, altered oscillations/propagation across cortico‑hippocampal/thalamocortical networks; potential neuroinflammatory and metabolic stress contributions (shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2).
Key Molecular Players
Anatomical locations (UBERON): neocortex, hippocampus, thalamus, brainstem autonomic centers (for cardiorespiratory control related to SUDEP risk) (shao2025spotlightonmechanism pages 1-2, gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 11-12).
Biological Processes (GO) disrupted
Regulation of cytosolic calcium ion concentration (GO:0051480) in astrocytes; mitochondrial oxidative phosphorylation (GO:0006119) and organelle function (GO:0005739) as metabolic modifiers (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2).
Cellular Components
Key compartments: axon initial segment and soma of inhibitory interneurons where Nav1.1 density impacts excitability; synaptic terminals mediating GABA release; astrocytic processes and microglial interfaces; mitochondria in neurons/glia (shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2).
Disease Progression
Phases: early febrile‑triggered onset; refractory multi‑seizure phase with developmental plateau/decline; chronic stage with comorbidity burden and mortality risk dominated by status epilepticus and SUDEP (gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 1-2, konrad2025morethanepilepsy—a pages 2-3).
Phenotypic Manifestations
Recent developments and latest research (2023–2024 priority) - Precision genetic therapies: antisense oligonucleotides that upregulate productive SCN1A transcripts (e.g., STK‑001/zorevunersen) show preclinical seizure/SUDEP reduction and early clinical seizure‑frequency improvements; AAV9‑based transcriptional activators (ETX101) and CRISPR/dCas9‑based SCN1A activation restore interneuron excitability and reduce seizures in DS models (Translational Psychiatry, 2025; Frontiers in Neuroscience, 2025; URLs: https://doi.org/10.1038/s41398-025-03304-8; https://doi.org/10.3389/fnins.2025.1634718) (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 12-13, zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2). - Interneuron‑targeted nuance: PV+ interneurons are a principal locus of Nav1.1 dependence; restoring Nav1.1 in inhibitory neurons rescues excitability and circuit stability in preclinical DS even after symptom onset (Frontiers in Neuroscience, 2025; https://doi.org/10.3389/fnins.2025.1634718) (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2). - Glial and metabolic roles: astrocyte Ca2+ signaling facilitation and mitochondrial/metabolic changes act as modifiers of seizure susceptibility and survival, suggesting therapeutic potential in glial/metabolic pathways (Frontiers in Neuroscience, 2025; https://doi.org/10.3389/fnins.2025.1634718) (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2). - Evolving therapeutic landscape: beyond conventional ASMs, newer approvals (stiripentol, cannabidiol, fenfluramine) are used in DS; serotonergic agents and cholesterol 24‑hydroxylase inhibition (soticlestat) are under study (J Clin Med, 2023; https://doi.org/10.3390/jcm12072532) (gao2023epilepsyindravet pages 1-2).
Current applications and real‑world implementations - Pharmacotherapy in practice: combination regimens including valproate/clobazam with adjuncts stiripentol, cannabidiol, or fenfluramine have become standard for convulsive seizures in DS, though developmental outcomes remain limited (J Clin Med, 2023; https://doi.org/10.3390/jcm12072532) (gao2023epilepsyindravet pages 1-2). - Non‑pharmacologic management: ketogenic diet and neuromodulation (e.g., VNS) are widely used as adjunctive strategies; benefits require careful cardiometabolic monitoring in DS due to SUDEP and potential cardiac vulnerability (Translational Psychiatry, 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 11-12). - Gene‑targeted trials: early‑phase investigations of ASOs (STK‑001/zorevunersen) and AAV9‑based activators (ETX101) are in or approaching clinical testing; early safety and signal on seizure frequency are reported for STK‑001 (Translational Psychiatry, 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 12-13).
Expert opinions and analysis from authoritative sources - Recent reviews emphasize a shift from symptomatic seizure control to mechanism‑driven interventions, centering SCN1A restoration strategies and interneuron‑targeted approaches to modify the disease course and potentially improve neurodevelopmental outcomes (Frontiers in Neuroscience, 2025; https://doi.org/10.3389/fnins.2025.1634718) (zhang2025dravetsyndromenovel pages 1-2). Parent/family stakeholder analyses identify pressing unmet needs—comprehensive understanding of SUDEP mechanisms and non‑epileptic comorbidities, adult‑onset course, and standardized outcome metrics beyond seizures (Clinical Epileptology, 2025; https://doi.org/10.1007/s10309-025-00785-x) (konrad2025morethanepilepsy—a pages 1-2).
Relevant statistics and data from recent studies - Incidence and prevalence: incidence approximately 1:15,700–1:40,900; DS is rare but consistently recognized across cohorts (Translational Psychiatry, 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 1-2). - Mortality/SUDEP burden: overall mortality is high; one analysis summarized SUDEP as accounting for nearly half of DS deaths, with noted incidence peaks at ages 1–3 and around 18 years (Translational Psychiatry, 2025; https://doi.org/10.1038/s41398-025-03304-8) (shao2025spotlightonmechanism pages 1-2). A parent‑led landscape review cites estimated mortality of 15.84/1000 person‑years and SUDEP of 9.32/1000 person‑years in DS, underscoring substantial risk (Clinical Epileptology, 2025; https://doi.org/10.1007/s10309-025-00785-x) (konrad2025morethanepilepsy—a pages 1-2).
Gene/protein annotations with ontology terms - SCN1A (HGNC:10585): voltage‑gated sodium channel alpha subunit Nav1.1; function: voltage‑gated sodium channel activity (GO:0005248); process: neuronal action potential (GO:0019228), GABAergic synaptic transmission (GO:0051932), trans‑synaptic signaling (GO:0099537); component: axon initial segment/somatic membrane; evidence (shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 1-2, zhang2025dravetsyndromenovel pages 21-22).
Phenotype associations (HP terms) - Seizures (HP:0001250), Febrile seizures (HP:0002373), Intellectual disability (HP:0001249), Autism spectrum feature (HP:0000717), Ataxia (HP:0001251), SUDEP/Sudden death (HP:0001738), Apnea (HP:0002878); evidence (gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 1-2, konrad2025morethanepilepsy—a pages 2-3, shao2025spotlightonmechanism pages 11-12).
Cell type involvement (CL terms) - GABAergic interneuron (CL:0000498), parvalbumin‑positive interneuron (CL:0002600), astrocyte (CL:0000127), microglia (CL:0000129); evidence (shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2).
Anatomical locations (UBERON terms) - Neocortex (UBERON:0000956), Hippocampus (UBERON:0001954), Thalamus (UBERON:0001897); evidence (shao2025spotlightonmechanism pages 1-2, gao2023epilepsyindravet pages 1-2, zhang2025dravetsyndromenovel pages 1-2).
Chemical entities (CHEBI terms) - Stiripentol (CHEBI:9483), Cannabidiol (CHEBI:69478), Fenfluramine (CHEBI:133010), Soticlestat (CHEBI:145562), Ketogenic diet proxy lipid (CHEBI:33284); evidence (gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 11-12).
Evidence items with PMIDs/DOIs and URLs - Shao et al., 2025, Translational Psychiatry. DOI: 10.1038/s41398-025-03304-8. URL: https://doi.org/10.1038/s41398-025-03304-8. Published Mar 2025. Topics: DS incidence; SUDEP mechanisms; ASO (STK‑001) and gene therapy prospects; non‑pharmacologic considerations (shao2025spotlightonmechanism pages 1-2, shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 12-13). - Zhang et al., 2025, Frontiers in Neuroscience. DOI: 10.3389/fnins.2025.1634718. URL: https://doi.org/10.3389/fnins.2025.1634718. Published Jul 2025. Topics: SCN1A molecular mechanisms; interneuron/glial and metabolic modifiers; diagnostics; ASO/CRISPRa/AAV strategies (zhang2025dravetsyndromenovel pages 1-2, zhang2025dravetsyndromenovel pages 21-22). - Gao et al., 2023, Journal of Clinical Medicine. DOI: 10.3390/jcm12072532. URL: https://doi.org/10.3390/jcm12072532. Published Mar 2023. Topics: therapeutic landscape including newer ASMs; precision and causative therapy directions; clinical burden (gao2023epilepsyindravet pages 1-2). - Konrad et al., 2025, Clinical Epileptology. DOI: 10.1007/s10309-025-00785-x. URL: https://doi.org/10.1007/s10309-025-00785-x. Published Nov 2025. Topics: stakeholder landscape; unmet needs; mortality/SUDEP estimates; pipeline (zorevunersen, ETX101, RT101) (konrad2025morethanepilepsy—a pages 1-2, konrad2025morethanepilepsy—a pages 2-3).
Structured knowledge for knowledge base population | Category | Entity/Term | Ontology ID (HGNC/GO/HP/CL/UBERON/CHEBI) | Role / Relevance in Dravet syndrome | Evidence (pqac IDs) | |---|---|---|---|---| | Gene | SCN1A | HGNC:10585 | Primary causal gene in ~70–90% of DS cases; encodes Nav1.1 whose haploinsufficiency reduces inhibitory interneuron excitability and drives network disinhibition | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, gao2023epilepsyindravet pages 1-2, zhang2025dravetsyndromenovel pages 21-22, konrad2025morethanepilepsy—a pages 2-3) | | Protein | Nav1.1 (alpha-1 sodium channel) | UniProt:Q15858 | Functional product of SCN1A; reduced Nav1.1 sodium currents in GABAergic interneurons (esp. PV+ cells) underlie seizures and E/I imbalance | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Cell type | GABAergic interneuron (parvalbumin-positive) | CL:0000498; CL:0002600 | Key affected cell type; hypoexcitability of PV+ interneurons leads to impaired inhibition and network hyperexcitability | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Cell type | Astrocyte | CL:0000127 | Non-neuronal contributor: altered astrocyte Ca2+ signaling and gliotransmission may exacerbate hyperexcitability and affect seizures/development | (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2, gao2023epilepsyindravet pages 1-2) | | Cell type | Microglia | CL:0000129 | Immune/glial modulation of network excitability and neuroinflammation implicated as modifier of disease severity | (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2) | | Anatomy | Hippocampus | UBERON:0001954 | Circuit node frequently implicated in seizure generation and neurodevelopmental comorbidity (memory/cognition) | (zhang2025dravetsyndromenovel pages 1-2, gao2023epilepsyindravet pages 1-2) | | Anatomy | Cortex | UBERON:0000956 | Widespread cortical disinhibition contributes to diverse seizure semiologies and cognitive/behavioral deficits | (zhang2025dravetsyndromenovel pages 1-2, gao2023epilepsyindravet pages 1-2) | | Anatomy | Thalamus | UBERON:0001897 | Thalamocortical circuits contribute to seizure propagation and generalized features in DS | (zhang2025dravetsyndromenovel pages 1-2, gao2023epilepsyindravet pages 1-2) | | Molecular function | Voltage-gated sodium channel activity | GO:0005248 | Core molecular activity disrupted by SCN1A variants; reduced sodium currents in interneurons impair action potential generation | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Biological process | GABAergic synaptic transmission | GO:0051932 | Impaired inhibitory synaptic signaling secondary to Nav1.1 loss drives excitatory/inhibitory imbalance | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Biological process | Neuronal action potential | GO:0019228 | Altered action potential firing in interneurons (reduced) and excitatory neurons (relative increase) underlies seizures | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2) | | Biological process | Trans-synaptic signaling (E/I balance proxy) | GO:0099537 | Represents disrupted excitatory/inhibitory balance across circuits in DS | (zhang2025dravetsyndromenovel pages 1-2, shao2025spotlightonmechanism pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Biological process | Regulation of cytosolic calcium ion concentration (astrocyte Ca2+ signaling) | GO:0051480 | Astrocytic Ca2+ dysregulation reported in Scn1a+/- models; may modulate seizures and development | (zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2) | | Cellular component / pathway | Mitochondrion / Oxidative phosphorylation | GO:0005739; GO:0006119 | Mitochondrial/metabolic deficits cited as disease modifiers that can worsen neuronal vulnerability and seizure susceptibility | (zhang2025dravetsyndromenovel pages 1-2, gao2023epilepsyindravet pages 1-2) | | Phenotype (HP) | Sudden unexpected death in epilepsy (SUDEP) / Sudden death | HP:0001738 | Elevated SUDEP risk in DS linked to high seizure burden, postictal cardiorespiratory dysfunction and possible cardiac susceptibility | (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Phenotype (HP) | Apnea / respiratory dysfunction | HP:0002878 | Postictal ventilatory compromise and sleep-associated events contribute to SUDEP risk | (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Phenotype (HP) | Seizures (convulsive) | HP:0001250 | Core clinical manifestation; febrile onset in infancy evolving to pharmacoresistant, mixed seizure types | (shao2025spotlightonmechanism pages 1-2, gao2023epilepsyindravet pages 1-2) | | Phenotype (HP) | Febrile seizures | HP:0002373 | Typical presenting seizure type in early infancy that prompts genetic evaluation for DS | (gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Phenotype (HP) | Intellectual disability | HP:0001249 | Common neurodevelopmental comorbidity linked to early-life seizures and network dysfunction | (gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Phenotype (HP) | Ataxia / gait abnormalities | HP:0001251 | Motor impairment (including crouch gait) described as characteristic comorbidity | (gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Phenotype (HP) | Autism spectrum features | HP:0000717 | Behavioral/autism-like traits frequent in DS and may relate to disrupted circuit development | (gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3) | | Chemical / Drug | Stiripentol | CHEBI:9483 | Approved adjunct with proven efficacy in DS convulsive seizures; part of current standard pharmacotherapy options | (gao2023epilepsyindravet pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Chemical / Drug | Cannabidiol (pharmaceutical-grade) | CHEBI:69478 | Approved therapy reducing convulsive seizure frequency in randomized trials | (gao2023epilepsyindravet pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Chemical / Drug | Fenfluramine | CHEBI:133010 | Approved and effective add-on therapy for DS convulsive seizures in RCTs | (gao2023epilepsyindravet pages 1-2, zhang2025dravetsyndromenovel pages 21-22) | | Chemical / Drug | Soticlestat | CHEBI:145562 | Investigational therapy targeting cholesterol 24-hydroxylase; explored for DS seizure reduction | (shao2025spotlightonmechanism pages 11-12, gao2023epilepsyindravet pages 1-2) | | Intervention | Ketogenic diet (proxy: lipid) | CHEBI:33284 | Non-pharmacologic therapy that can reduce seizure burden but requires metabolic/cardiac monitoring | (shao2025spotlightonmechanism pages 11-12, gao2023epilepsyindravet pages 1-2) | | Therapeutic modality | ASO therapeutic (e.g., STK-001 / zorevunersen) | N/A (ASO therapeutic) | Antisense oligonucleotide strategies (TANGO/STK-001) aim to upregulate productive SCN1A transcript and restore Nav1.1 expression; preclinical and early clinical signals reported | (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 12-13, zhang2025dravetsyndromenovel pages 21-22) | | Therapeutic modality | AAV gene therapy (e.g., ETX101, AAV9-based) | N/A (AAV gene therapy) | Viral-vector transcriptional activation of SCN1A in inhibitory neurons showed seizure reduction and reduced SUDEP in preclinical models; clinical translation underway | (shao2025spotlightonmechanism pages 12-13, zhang2025dravetsyndromenovel pages 21-22, shao2025spotlightonmechanism pages 11-12) |
Table: Concise table mapping genes, proteins, cell types, processes, phenotypes, anatomical sites, drugs, and therapeutic modalities to ontology identifiers and primary evidence IDs; useful for ontology annotation and evidence-linked knowledgebase population.
Disease progression narrative (from trigger to clinical manifestation) - Trigger: genetic SCN1A LoF leads to Nav1.1‑dependent interneuron hypoexcitability. - Early phase: febrile stimulus lowers threshold → prolonged hemiclonic/status seizures in infancy; nascent E/I imbalance in key cortical/hippocampal/thalamic circuits (gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 1-2). - Expansion: recurrent seizures and network instability propagate to diverse semiologies; neurodevelopmental plateau/decline with cognitive, behavioral, gait/motor, sleep/breathing problems (gao2023epilepsyindravet pages 1-2, konrad2025morethanepilepsy—a pages 2-3). - Complications: high risk of status epilepticus and SUDEP, particularly during sleep/early morning, mediated by postictal ventilatory dysfunction and possible cardiac arrhythmias; risk modulated by seizure control and comorbidities (shao2025spotlightonmechanism pages 1-2, shao2025spotlightonmechanism pages 11-12, konrad2025morethanepilepsy—a pages 2-3).
Therapeutic implications drawn from mechanisms - Avoid broad sodium channel blockers that can worsen DS; prioritize therapies enhancing inhibition or restoring SCN1A/Nav1.1 function (shao2025spotlightonmechanism pages 11-12, gao2023epilepsyindravet pages 1-2). - Employ DS‑specific adjuncts (stiripentol, cannabidiol, fenfluramine) while recognizing limited impact on neurodevelopmental outcomes; consider metabolic and neuromodulatory adjuncts with vigilant cardiorespiratory monitoring (gao2023epilepsyindravet pages 1-2, shao2025spotlightonmechanism pages 11-12). - For disease modification, gene‑targeted strategies (ASOs, AAV‑based transcriptional activation, CRISPRa) are the leading candidates with preclinical seizure/SUDEP rescue and initial clinical tolerability/signal; trials should stratify by variant class and consider interneuron‑specific targeting (shao2025spotlightonmechanism pages 11-12, shao2025spotlightonmechanism pages 12-13, zhang2025dravetsyndromenovel pages 21-22, zhang2025dravetsyndromenovel pages 1-2).
Limitations and gaps - Precise links from molecular lesions to adult DS course and non‑epileptic comorbidities require further mechanistic work; standardized outcome metrics beyond seizures are needed in trials (konrad2025morethanepilepsy—a pages 1-2). Larger controlled studies for neuromodulatory and metabolic interventions, and rigorous validation of gene therapies in humans, remain priorities (shao2025spotlightonmechanism pages 11-12, zhang2025dravetsyndromenovel pages 1-2).
Overall conclusion DS pathophysiology centers on SCN1A/Nav1.1‑mediated interneuron dysfunction and circuit‑level E/I imbalance, with glial and metabolic modifiers. Recent (2023–2025) advances validate disease‑modifying strategies that restore SCN1A function, alongside optimized seizure‑directed regimens. Given high SUDEP risk and multisystem comorbidities, integrated care with precision therapeutics, vigilant cardiorespiratory management, and comprehensive developmental support is essential (shao2025spotlightonmechanism pages 1-2, shao2025spotlightonmechanism pages 11-12, zhang2025dravetsyndromenovel pages 1-2, konrad2025morethanepilepsy—a pages 2-3, gao2023epilepsyindravet pages 1-2).
References
(shao2025spotlightonmechanism pages 1-2): WeiHui Shao, Lu Liu, JiaXuan Gu, Yue Yang, YaXuan Wu, ZhuoYue Zhang, Qing Xu, YuLing Wang, Yue Shen, LeYuan Gu, Yuan Cheng, and HongHai Zhang. Spotlight on mechanism of sudden unexpected death in epilepsy in dravet syndrome. Translational Psychiatry, Mar 2025. URL: https://doi.org/10.1038/s41398-025-03304-8, doi:10.1038/s41398-025-03304-8. This article has 4 citations and is from a peer-reviewed journal.
(gao2023epilepsyindravet pages 1-2): Chao Gao, Mikolaj Pielas, Fuyong Jiao, Daoqi Mei, Xiaona Wang, Katarzyna Kotulska, and Sergiusz Jozwiak. Epilepsy in dravet syndrome—current and future therapeutic opportunities. Journal of Clinical Medicine, 12:2532, Mar 2023. URL: https://doi.org/10.3390/jcm12072532, doi:10.3390/jcm12072532. This article has 37 citations and is from a poor quality or predatory journal.
(konrad2025morethanepilepsy—a pages 2-3): Carsten Konrad, Simona Borroni, Serpil Budak, Silke Flege, and Daniel Kiper. More than epilepsy—a parent-initiated collaborative analysis of the research landscape and research needs in dravet syndrome. Clinical Epileptology, Nov 2025. URL: https://doi.org/10.1007/s10309-025-00785-x, doi:10.1007/s10309-025-00785-x. This article has 0 citations and is from a poor quality or predatory journal.
(zhang2025dravetsyndromenovel pages 21-22): Guirui Zhang, Shupeng Huang, Mingzhen Wei, Yongmo Wu, Zhengyi Xie, and Jin Wang. Dravet syndrome: novel insights into scn1a-mediated epileptic neurodevelopmental disorders within the molecular diagnostic-therapeutic framework. Frontiers in Neuroscience, Jul 2025. URL: https://doi.org/10.3389/fnins.2025.1634718, doi:10.3389/fnins.2025.1634718. This article has 3 citations and is from a peer-reviewed journal.
(zhang2025dravetsyndromenovel pages 1-2): Guirui Zhang, Shupeng Huang, Mingzhen Wei, Yongmo Wu, Zhengyi Xie, and Jin Wang. Dravet syndrome: novel insights into scn1a-mediated epileptic neurodevelopmental disorders within the molecular diagnostic-therapeutic framework. Frontiers in Neuroscience, Jul 2025. URL: https://doi.org/10.3389/fnins.2025.1634718, doi:10.3389/fnins.2025.1634718. This article has 3 citations and is from a peer-reviewed journal.
(shao2025spotlightonmechanism pages 11-12): WeiHui Shao, Lu Liu, JiaXuan Gu, Yue Yang, YaXuan Wu, ZhuoYue Zhang, Qing Xu, YuLing Wang, Yue Shen, LeYuan Gu, Yuan Cheng, and HongHai Zhang. Spotlight on mechanism of sudden unexpected death in epilepsy in dravet syndrome. Translational Psychiatry, Mar 2025. URL: https://doi.org/10.1038/s41398-025-03304-8, doi:10.1038/s41398-025-03304-8. This article has 4 citations and is from a peer-reviewed journal.
(shao2025spotlightonmechanism pages 12-13): WeiHui Shao, Lu Liu, JiaXuan Gu, Yue Yang, YaXuan Wu, ZhuoYue Zhang, Qing Xu, YuLing Wang, Yue Shen, LeYuan Gu, Yuan Cheng, and HongHai Zhang. Spotlight on mechanism of sudden unexpected death in epilepsy in dravet syndrome. Translational Psychiatry, Mar 2025. URL: https://doi.org/10.1038/s41398-025-03304-8, doi:10.1038/s41398-025-03304-8. This article has 4 citations and is from a peer-reviewed journal.
(konrad2025morethanepilepsy—a pages 1-2): Carsten Konrad, Simona Borroni, Serpil Budak, Silke Flege, and Daniel Kiper. More than epilepsy—a parent-initiated collaborative analysis of the research landscape and research needs in dravet syndrome. Clinical Epileptology, Nov 2025. URL: https://doi.org/10.1007/s10309-025-00785-x, doi:10.1007/s10309-025-00785-x. This article has 0 citations and is from a poor quality or predatory journal.