SNAP25-Related Developmental and Epileptic Encephalopathy

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Inheritance

1

Autosomal Dominant (De Novo) HP:0000006

The disorder arises from de novo heterozygous SNAP25 missense or loss-of-function variants.

Autosomal dominant inheritance

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25."

Establishes the de novo dominant genetic basis across a patient cohort.

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Discussions and Knowledge Gaps

3

For a given pathogenic SNAP25 variant, what determines whether it acts by simple loss of function (haploinsufficiency, reduced evoked release) versus a dominant-negative or gain-of-function mechanism (altered SNARE zippering or increased complex-binding affinity), and does the direction of effect predict the clinical subphenotype (DEE versus milder intellectual disability versus ataxic or myasthenic features)?

KNOWLEDGE GAP OPEN gap_snap25_direction_of_effect

Attached to

pathophysiology#SNAP-25 SNARE Assembly Defect pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

SNAP25-DEE is caused by a mix of missense and loss-of-function de novo variants, but structural modeling in the defining cohort could only predict "possible functional defects" without resolving whether release is reduced by haploinsufficiency or by a dominant-negative variant that is incorporated into the SNARE complex and poisons it. The blind-drunk mouse shows that a SNAP-25 missense change can act paradoxically by *increasing* SNARE-complex binding affinity rather than abolishing it, so direction of effect cannot be assumed from the variant class alone. This matters therapeutically: allele-silencing or protein-replacement strategies help only true loss of function, whereas a dominant-negative allele may need selective knockdown of the mutant transcript.

Proposed experiments

SNAP25 variant direction-of-effect release panel

variant functional-classification and rescue experiment

exp_snap25_variant_direction_release_panel

Express representative SNAP25 DEE variants (missense and loss-of-function) in Snap25-null neurons alone and co-expressed with wild-type SNAP-25 in an isogenic background, then measure evoked release and SNARE-complex assembly to classify each variant as loss-of-function versus dominant-negative.

Perturbations

SNAP25 variant expression on null background

pathophysiology#SNAP-25 SNARE Assembly Defect

Introduce each DEE variant into Snap25-null neurons, with and without co-expressed wild-type SNAP-25, to test for haploinsufficiency versus dominant interference.

SNAP25 hgnc:11132

Readouts

Evoked release and SNARE assembly

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

calcium-dependent activation of synaptic vesicle fusion GO:0099502 ↓ DECREASED synaptic vesicle exocytosis GO:0016079 ↓ DECREASED

patch-clamp electrophysiology assay co-immunoprecipitation assay

Direction: NEGATIVE

Controls

Wild-type SNAP-25 rescue

Snap25-null neurons rescued with wild-type human SNAP-25.

Null baseline

Snap25-null neurons without rescue as the loss-of-function floor.

Decision criterion

A variant is loss-of-function if it fails to restore evoked release on the null background and does not depress wild-type-mediated release when co-expressed; it is dominant-negative if co-expression with wild-type SNAP-25 reduces release below the wild-type-only level.

Would support

pathophysiology#SNAP-25 SNARE Assembly Defect pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

Show evidence (3 references)

PMID:33299146 SUPPORT Human Clinical

"Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex."

Shows that the human cohort establishes disruption of SNAP-25 or its SNARE interactions but does not resolve the direction of effect (loss versus dominant-negative) for individual variants.

PMID:17283335 SUPPORT Model Organism

"The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials."

Demonstrates that a SNAP-25 missense variant can act by increasing, not abolishing, SNARE-complex binding affinity, showing the direction of effect is not predictable from variant class and motivating the gap.

PMID:32559416 SUPPORT Other

"We argue that disease severity generally scales with functional redundancy"

Frames the SNAREopathy expectation that mechanism and severity vary with redundancy, supporting the need to resolve per-variant direction of effect.

How much of the cortical hyperexcitability and seizure phenotype in SNAP25-DEE arises from impaired calcium-triggered vesicle fusion (release failure) versus SNAP-25's separable, non-fusion modulation of presynaptic voltage-gated calcium and potassium channels (a channelopathy-like change in intrinsic excitability)?

OPEN QUESTION OPEN gap_snap25_channel_modulation_vs_release_failure

Attached to

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

The curated causal chain routes the phenotype through reduced SNARE-mediated release, but SNAP-25 has well-described roles beyond exocytosis, including negative modulation of voltage-gated calcium channels and interactions that tune neuronal excitability. Because DEE variants sit in the same protein that performs both jobs, the seizure phenotype could reflect a release deficit, a channelopathy-like intrinsic-excitability shift, or both — and the balance may differ by variant and neuron type. Distinguishing these arms is needed before excitability-targeted therapy is rationalized, and it is not resolved by the current release-centric evidence.

Proposed experiments

SNAP25 release versus intrinsic-excitability dissection

electrophysiological mechanism-dissection experiment

exp_snap25_release_vs_intrinsic_excitability

In neurons expressing SNAP25 DEE variants, separately quantify evoked synaptic release and cell-autonomous intrinsic excitability (voltage-gated calcium and potassium current density, action-potential threshold and firing) to apportion the excitability change between fusion failure and channel modulation.

Perturbations

SNAP25 DEE variant expression

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

Express DEE variants in neurons and compare against wild-type SNAP-25 and null controls.

SNAP25 hgnc:11132

Readouts

Evoked synaptic transmission

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

chemical synaptic transmission GO:0007268 ↓ DECREASED

patch-clamp electrophysiology assay

Direction: NEGATIVE

Intrinsic excitability and channel currents

pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

voltage-clamp current-density assay current-clamp firing assay

Direction: POSITIVE

Controls

Wild-type SNAP-25

Neurons expressing wild-type SNAP-25.

Snap25-null

Null neurons isolating the loss-of-function reference.

Decision criterion

The channel-modulation arm is supported if DEE variants shift intrinsic excitability (altered calcium or potassium current density, firing, or threshold) beyond what is accounted for by the measured reduction in evoked release; otherwise the phenotype is release-dominated.

Would support

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

Show evidence (2 references)

PMID:17283335 SUPPORT Model Organism

"The causative I67T missense mutation results in increased binding affinities within the SNARE complex, impaired exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells, and a reduction in the amplitude of evoked cortical excitatory postsynaptic potentials."

Documents that a SNAP-25 variant reduces evoked cortical release (the fusion arm) but does not measure the channel-modulation contribution to excitability, leaving the relative weighting open.

PMID:32559416 SUPPORT Other

"subtle differences in components being rate limiting in different types of neurons helps to explain the main symptoms."

Supports the expectation that SNARE-component effects are neuron-type dependent, consistent with a mixed release-plus-excitability contribution that must be disentangled.

Do existing Snap25 point-mutant mouse models, which reproduce ataxia, sensorimotor-gating deficits, and reduced cortical release, faithfully model the human SNAP25-DEE trajectory of before-age-two epileptic encephalopathy with intellectual disability, or do they capture only a partial, non-epileptic slice of the human phenotype?

HUMAN MODEL MISMATCH OPEN gap_snap25_mouse_model_human_dee_fidelity

Attached to

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

The strongest mechanistic in vivo evidence for SNAP-25 dysfunction comes from the blind-drunk I67T mouse, whose overt phenotype is ataxia and impaired sensorimotor gating with reduced evoked cortical release — features linked to psychiatric rather than epileptic disease. Human SNAP25-DEE, by contrast, is defined by early-onset epilepsy and intellectual disability with onset mostly before age two. Whether the mouse recapitulates the human epileptic encephalopathy trajectory, or only the synaptic and motor substrate, is the open translational question; this determines whether the model is a valid platform for testing DEE-directed therapies.

Proposed experiments

SNAP25 patient-variant knock-in epileptogenesis phenotyping

patient-variant knock-in mouse phenotyping experiment

exp_snap25_ki_epileptogenesis_phenotyping

Generate knock-in mice carrying recurrent human SNAP25 DEE variants and phenotype for spontaneous seizures and epileptiform EEG, developmental cognitive assays, and cortical excitatory/inhibitory balance, comparing the trajectory and age of onset against the human before-age-two course.

Perturbations

Human DEE variant knock-in

pathophysiology#SNAP-25 SNARE Assembly Defect

Introduce a recurrent human SNAP25 DEE variant at the mouse locus.

SNAP25 hgnc:11132

Readouts

Seizures and cortical excitability

pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

chemical synaptic transmission GO:0007268 ⚠ ABNORMAL

video-EEG seizure monitoring

Direction: POSITIVE

Controls

Wild-type littermates

Littermate controls without the knock-in variant.

Decision criterion

The model faithfully represents SNAP25-DEE if knock-in mice develop early spontaneous seizures with epileptiform EEG and developmental cognitive deficits on a timeline analogous to the human before-age-two onset; absence of an epileptic phenotype indicates a human-model mismatch limited to the synaptic/motor substrate.

Would support

pathophysiology#Impaired SNARE-Mediated Vesicle Fusion pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

Show evidence (2 references)

PMID:17283335 SUPPORT Model Organism

"The mice also display ataxia and impaired sensorimotor gating, a phenotype which has been associated with psychiatric disorders in humans."

Establishes the model-organism phenotype (ataxia, sensorimotor gating) whose correspondence to the human DEE trajectory is uncertain.

PMID:33299146 SUPPORT Human Clinical

"intellectual disability and early-onset epilepsy mostly occurring before the age of two years."

States the human clinical trajectory against which the mouse model's fidelity must be judged.

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Pathophysiology

3

SNAP-25 SNARE Assembly Defect

De novo missense and loss-of-function variants in SNAP25 impair SNAP-25, a core t-SNARE of the neuronal fusion machine. Structural modeling of disease variants predicts defects in SNAP-25 itself or in its interaction with the other SNARE components (syntaxin-1, synaptobrevin-2), degrading assembly of the SNARE complex that executes vesicle fusion.

neuron CL:0000540

synaptic vesicle cycle GO:0099504 ⚠ ABNORMAL

brain UBERON:0000955

Downstream

Impaired SNARE-Mediated Vesicle Fusion

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex."

Establishes that disease variants disrupt SNAP-25 or its SNARE-complex interactions, the molecular lesion of this node.

Impaired SNARE-Mediated Vesicle Fusion

SNAP-25 is one of the three core SNAREs whose zippering, triggered by the calcium sensor synaptotagmin-1, fuses the synaptic vesicle with the presynaptic membrane. Impaired SNAP-25 function degrades SNARE-complex assembly and reduces calcium-triggered neurotransmitter release. This is the module's key conformance target — the fusion-machinery arm.

neuron CL:0000540

calcium-dependent activation of synaptic vesicle fusion GO:0099502 ↓ DECREASED synaptic vesicle exocytosis GO:0016079 ↓ DECREASED

Downstream

Cortical Excitation-Inhibition Imbalance and Seizures

Show evidence (2 references)

PMID:32559416 SUPPORT Other

"Neuronal SNAREs and their key regulators together drive synaptic vesicle exocytosis and synaptic transmission as a single integrated membrane fusion machine."

Establishes SNAP-25 (a core SNARE) as part of the integrated fusion machine impaired in this disorder.

PMID:33299146 SUPPORT Human Clinical

"Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex."

Links the disease variants specifically to impaired SNARE-complex function, the fusion step.

Cortical Excitation-Inhibition Imbalance and Seizures

Reduced and imbalanced neurotransmitter release disturbs cortical excitatory/inhibitory balance, producing neuronal hyperexcitability and an early-onset epilepsy, together with impaired activity-dependent neurodevelopment manifesting as intellectual disability.

neuron CL:0000540

chemical synaptic transmission GO:0007268 ⚠ ABNORMAL

neocortex UBERON:0001950

Downstream

Epilepsy

Intellectual Disability

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy."

Documents early-onset epilepsy and intellectual disability as the core clinical outcomes.

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

5

Nervous System 3

Intellectual Disability HP:0001249

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE"

Documents intellectual disability as a core symptom.

Movement Disorder Abnormality of movement HP:0100022

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy."

Documents movement disorders as a recurrent feature.

Cerebral Atrophy HP:0002059

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy."

Documents brain atrophy as a recurrent finding.

Other 2

Epilepsy Epileptic encephalopathy HP:0200134

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years."

Documents early-onset epilepsy as a core symptom with onset before age two.

Cerebral Visual Impairment HP:0100704

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy."

Documents cerebral visual impairment as a recurrent feature.

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Genetic Associations

1

SNAP25 (Loss-of-Function and Missense Mutations)

Gene: SNAP25 hgnc:11132 variant_origin: GERMLINE

Autosomal Dominant (De Novo)

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review."

Defines the heterozygous missense and loss-of-function variant spectrum.

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Medical Actions

3

Antiseizure Medication

Action: Pharmacotherapy NCIT:C15986

Agent: levetiracetam CHEBI:6437

Seizures are managed with antiseizure medications; response is variable. No agent corrects the underlying SNARE-assembly defect.

Supportive and Developmental Care

Action: Supportive Care NCIT:C15747

Multidisciplinary supportive care, including developmental therapies and vision support for cerebral visual impairment, is the mainstay.

Genetic Counseling

Action: genetic counseling Ontology label: Genetic Counseling NCIT:C15240

Genetic counseling addresses the de novo dominant mechanism and generally low recurrence risk.

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Diagnosis

1

SNAP25 Molecular Diagnosis

Diagnosis is established by identifying a de novo heterozygous pathogenic SNAP25 variant in a child with early-onset epilepsy and intellectual disability.

molecular genetic testing NCIT:C19770

Results: A de novo pathogenic SNAP25 variant establishes the diagnosis.

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25."

Molecular identification of de novo SNAP25 variants establishes the diagnosis.

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Progression

1

Infancy to Early Childhood

Onset is typically before age two with early-onset epilepsy and evolving intellectual disability; movement disorders, cerebral visual impairment, and brain atrophy are recurrent.

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"intellectual disability and early-onset epilepsy mostly occurring before the age of two years."

Documents onset before age two.

📊

Prevalence

1

Worldwide

Unknown Ultra Rare

Ultra-rare monogenic developmental and epileptic encephalopathy; precise population prevalence not established.

🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from SNAP25-Related Developmental and Epileptic Encephalopathy:

Other SNAREopathies and synaptic vesicle cycle disorders

Overlapping Features Other SNARE-machinery and synaptic vesicle cycle disorders (STXBP1, STX1B, VAMP2, UNC13A) share early-onset epilepsy and developmental impairment and are distinguished by molecular testing.

Distinguishing Features

A de novo SNAP25 variant favors this disorder.
A variant in another SNARE/vesicle-cycle gene favors the corresponding SNAREopathy.

Show evidence (1 reference)

PMID:33299146 SUPPORT Human Clinical

"These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2."

Establishes the overlapping SNAREopathy differential diagnosis.

{ }

Source YAML

click to show

name: SNAP25-Related Developmental and Epileptic Encephalopathy
creation_date: "2026-07-06T00:00:00Z"
description: >-
  A developmental and epileptic encephalopathy caused by de novo variants in
  SNAP25, which encodes SNAP-25 (synaptosomal-associated protein 25), a core
  plasma-membrane (t-)SNARE that assembles with syntaxin-1 and synaptobrevin-2 to
  drive calcium-triggered synaptic vesicle fusion. Pathogenic missense and
  loss-of-function variants impair SNARE-complex function, reducing evoked
  neurotransmitter release. The core phenotype is intellectual disability and
  early-onset epilepsy (usually before age two), with recurrent movement
  disorders, cerebral visual impairment, and brain atrophy. It is one of the
  SNAREopathies and a synaptic vesicle cycle disorder, representing — with STXBP1,
  STX1B, and VAMP2 — the fusion-machinery arm of the cycle.
category: Mendelian
parents:
- Neurodevelopmental Disorder
- Epileptic Encephalopathy
synonyms:
- SNAP25-DEE
- developmental and epileptic encephalopathy 117
- DEE117
- congenital myasthenic syndrome 18 (formerly)
- CMS18 (formerly)
disease_term:
  preferred_term: SNAP25-related developmental and epileptic encephalopathy
  term:
    id: MONDO:0014590
    label: congenital myasthenic syndrome 18
notes: >-
  The disease_term label reads "congenital myasthenic syndrome 18" only because
  that is MONDO:0014590's current canonical label, which term validation requires
  be reproduced verbatim. It is NOT a mis-binding: OMIM:616330 (to which
  MONDO:0014590 is equivalent) has been retitled "developmental and epileptic
  encephalopathy-117 (DEE117)", with "myasthenic syndrome, congenital, 18"
  retained only as a former title, and its OMIM definition is now the DEE
  description drawn from Klockner et al. 2021 (PMID:33299146) — the same cohort
  this entry curates. OMIM models one MIM number as one phenotype concept, so
  the myasthenic presentation is a variant-associated feature of this spectrum
  rather than a separate disease. MONDO triage concluded the two titles denote
  one concept, and a rename and re-parent of MONDO:0014590 has been proposed but
  not yet made (monarch-initiative/mondo#10532, still open); update this label if
  and when that lands. Do not "correct" the binding by moving it to
  MONDO:0032678, which is the unrelated GLS/glutaminase entity.

  Scope: because MONDO:0014590 denotes the whole OMIM:616330 concept, this entry
  formally spans the myasthenic presentation as well, but deliberately curates
  only the developmental and epileptic encephalopathy arm — the 23-patient
  Klockner cohort, in which most individuals had no prominent neuromuscular
  symptoms. The presynaptic myasthenic arm, described in the original SNAP25B
  p.Ile67Asn index case, is under-curated here and is not represented in the
  phenotypes below.
prevalence:
- population: Worldwide
  measure_type: UNKNOWN
  prevalence_class: ULTRA_RARE
  notes: >-
    Ultra-rare monogenic developmental and epileptic encephalopathy; precise population prevalence not established.
references:
- reference: PMID:33299146
  title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
- reference: PMID:32559416
  title: "SNAREopathies: Diversity in Mechanisms and Symptoms."
inheritance:
- name: Autosomal Dominant (De Novo)
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    The disorder arises from de novo heterozygous SNAP25 missense or
    loss-of-function variants.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The cohort comprises 23 individuals with pathogenic or likely pathogenic de
      novo variants in SNAP25.
    explanation: >-
      Establishes the de novo dominant genetic basis across a patient cohort.
pathophysiology:
- name: SNAP-25 SNARE Assembly Defect
  conforms_to: "synaptic_vesicle_cycle#Synaptic Vesicle Cycle Protein Deficiency"
  description: >-
    De novo missense and loss-of-function variants in SNAP25 impair SNAP-25, a core
    t-SNARE of the neuronal fusion machine. Structural modeling of disease variants
    predicts defects in SNAP-25 itself or in its interaction with the other SNARE
    components (syntaxin-1, synaptobrevin-2), degrading assembly of the SNARE
    complex that executes vesicle fusion.
  role: trigger
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: synaptic vesicle cycle
    term:
      id: GO:0099504
      label: synaptic vesicle cycle
    modifier: ABNORMAL
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Structural modeling for all variants predicted possible functional defects
      concerning SNAP25 or impaired interaction with other components of the SNARE
      complex.
    explanation: >-
      Establishes that disease variants disrupt SNAP-25 or its SNARE-complex
      interactions, the molecular lesion of this node.
  downstream:
  - target: Impaired SNARE-Mediated Vesicle Fusion
    causal_link_type: DIRECT
- name: Impaired SNARE-Mediated Vesicle Fusion
  conforms_to: "synaptic_vesicle_cycle#Impaired Calcium-Triggered SNARE-Mediated Vesicle Fusion"
  description: >-
    SNAP-25 is one of the three core SNAREs whose zippering, triggered by the
    calcium sensor synaptotagmin-1, fuses the synaptic vesicle with the presynaptic
    membrane. Impaired SNAP-25 function degrades SNARE-complex assembly and reduces
    calcium-triggered neurotransmitter release. This is the module's key conformance
    target — the fusion-machinery arm.
  role: central_effector
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: calcium-dependent activation of synaptic vesicle fusion
    term:
      id: GO:0099502
      label: calcium-dependent activation of synaptic vesicle fusion
    modifier: DECREASED
  - preferred_term: synaptic vesicle exocytosis
    term:
      id: GO:0016079
      label: synaptic vesicle exocytosis
    modifier: DECREASED
  evidence:
  - reference: PMID:32559416
    reference_title: "SNAREopathies: Diversity in Mechanisms and Symptoms."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Neuronal SNAREs and their key regulators together drive synaptic vesicle
      exocytosis and synaptic transmission as a single integrated membrane fusion
      machine.
    explanation: >-
      Establishes SNAP-25 (a core SNARE) as part of the integrated fusion machine
      impaired in this disorder.
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Structural modeling for all variants predicted possible functional defects
      concerning SNAP25 or impaired interaction with other components of the SNARE
      complex.
    explanation: >-
      Links the disease variants specifically to impaired SNARE-complex function,
      the fusion step.
  downstream:
  - target: Cortical Excitation-Inhibition Imbalance and Seizures
    causal_link_type: DIRECT
- name: Cortical Excitation-Inhibition Imbalance and Seizures
  conforms_to: "epilepsy_excitation_inhibition_imbalance#Neuronal Hyperexcitability and Hypersynchrony"
  description: >-
    Reduced and imbalanced neurotransmitter release disturbs cortical
    excitatory/inhibitory balance, producing neuronal hyperexcitability and an
    early-onset epilepsy, together with impaired activity-dependent neurodevelopment
    manifesting as intellectual disability.
  role: effector
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: chemical synaptic transmission
    term:
      id: GO:0007268
      label: chemical synaptic transmission
    modifier: ABNORMAL
  locations:
  - preferred_term: neocortex
    term:
      id: UBERON:0001950
      label: neocortex
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Intellectual disability and early-onset epilepsy were identified as the core
      symptoms of SNAP25-DEE, with recurrent findings of movement disorders,
      cerebral visual impairment, and brain atrophy.
    explanation: >-
      Documents early-onset epilepsy and intellectual disability as the core
      clinical outcomes.
  downstream:
  - target: Epilepsy
    causal_link_type: DIRECT
  - target: Intellectual Disability
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Impaired activity-dependent synaptic transmission during development.
phenotypes:
- name: Epilepsy
  category: Clinical
  description: >-
    Early-onset epilepsy, a core symptom, most often beginning before age two.
  diagnostic: true
  phenotype_term:
    preferred_term: Epileptic encephalopathy
    term:
      id: HP:0200134
      label: Epileptic encephalopathy
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We provide a comprehensive description of SNAP25-DEE with intellectual
      disability and early-onset epilepsy mostly occurring before the age of two
      years.
    explanation: >-
      Documents early-onset epilepsy as a core symptom with onset before age two.
- name: Intellectual Disability
  category: Clinical
  description: >-
    Intellectual disability is a core symptom of SNAP25-DEE.
  diagnostic: true
  phenotype_term:
    preferred_term: Intellectual disability
    term:
      id: HP:0001249
      label: Intellectual disability
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Intellectual disability and early-onset epilepsy were identified as the core
      symptoms of SNAP25-DEE
    explanation: >-
      Documents intellectual disability as a core symptom.
- name: Movement Disorder
  category: Clinical
  description: >-
    Movement disorders are a recurrent feature.
  phenotype_term:
    preferred_term: Abnormality of movement
    term:
      id: HP:0100022
      label: Abnormality of movement
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      with recurrent findings of movement disorders, cerebral visual impairment,
      and brain atrophy.
    explanation: >-
      Documents movement disorders as a recurrent feature.
- name: Cerebral Visual Impairment
  category: Clinical
  description: >-
    Cerebral (cortical) visual impairment is a recurrent feature.
  phenotype_term:
    preferred_term: Cerebral visual impairment
    term:
      id: HP:0100704
      label: Cerebral visual impairment
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      with recurrent findings of movement disorders, cerebral visual impairment,
      and brain atrophy.
    explanation: >-
      Documents cerebral visual impairment as a recurrent feature.
- name: Cerebral Atrophy
  category: Clinical
  description: >-
    Brain atrophy is a recurrent neuroimaging finding.
  phenotype_term:
    preferred_term: Cerebral atrophy
    term:
      id: HP:0002059
      label: Cerebral atrophy
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      with recurrent findings of movement disorders, cerebral visual impairment,
      and brain atrophy.
    explanation: >-
      Documents brain atrophy as a recurrent finding.
genetic:
- name: SNAP25
  gene_term:
    preferred_term: SNAP25
    term:
      id: hgnc:11132
      label: SNAP25
  association: Loss-of-Function and Missense Mutations
  presence: Positive
  variant_origin: GERMLINE
  inheritance:
  - name: Autosomal Dominant (De Novo)
    inheritance_term:
      preferred_term: Autosomal dominant inheritance
      term:
        id: HP:0000006
        label: Autosomal dominant inheritance
  notes: >-
    De novo heterozygous missense and loss-of-function variants in SNAP25 impair
    SNAP-25 function or its interaction with the other SNARE-complex components.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Individuals harboring heterozygous missense or loss-of-function variants in
      SNAP25 were assembled through collaboration with international colleagues,
      matchmaking platforms, and literature review.
    explanation: >-
      Defines the heterozygous missense and loss-of-function variant spectrum.
diagnosis:
- name: SNAP25 Molecular Diagnosis
  description: >-
    Diagnosis is established by identifying a de novo heterozygous pathogenic
    SNAP25 variant in a child with early-onset epilepsy and intellectual disability.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
    qualifiers:
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: SNAP25
        term:
          id: hgnc:11132
          label: SNAP25
  results: A de novo pathogenic SNAP25 variant establishes the diagnosis.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The cohort comprises 23 individuals with pathogenic or likely pathogenic de
      novo variants in SNAP25.
    explanation: >-
      Molecular identification of de novo SNAP25 variants establishes the diagnosis.
differential_diagnoses:
- name: Other SNAREopathies and synaptic vesicle cycle disorders
  description: >-
    Other SNARE-machinery and synaptic vesicle cycle disorders (STXBP1, STX1B,
    VAMP2, UNC13A) share early-onset epilepsy and developmental impairment and are
    distinguished by molecular testing.
  distinguishing_features:
  - A de novo SNAP25 variant favors this disorder.
  - A variant in another SNARE/vesicle-cycle gene favors the corresponding SNAREopathy.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      These core symptoms and additional recurrent phenotypes show an overlap to
      genes encoding other components or associated proteins of the SNARE complex
      such as STX1B, STXBP1, or VAMP2.
    explanation: >-
      Establishes the overlapping SNAREopathy differential diagnosis.
progression:
- phase: Infancy to Early Childhood
  notes: >-
    Onset is typically before age two with early-onset epilepsy and evolving
    intellectual disability; movement disorders, cerebral visual impairment, and
    brain atrophy are recurrent.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      intellectual disability and early-onset epilepsy mostly occurring before the
      age of two years.
    explanation: >-
      Documents onset before age two.
treatments:
- name: Antiseizure Medication
  description: >-
    Seizures are managed with antiseizure medications; response is variable. No
    agent corrects the underlying SNARE-assembly defect.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: levetiracetam
      term:
        id: CHEBI:6437
        label: levetiracetam
- name: Supportive and Developmental Care
  description: >-
    Multidisciplinary supportive care, including developmental therapies and
    vision support for cerebral visual impairment, is the mainstay.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
- name: Genetic Counseling
  description: >-
    Genetic counseling addresses the de novo dominant mechanism and generally low
    recurrence risk.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
discussions:
- discussion_id: gap_snap25_direction_of_effect
  prompt: >-
    For a given pathogenic SNAP25 variant, what determines whether it acts by
    simple loss of function (haploinsufficiency, reduced evoked release) versus a
    dominant-negative or gain-of-function mechanism (altered SNARE zippering or
    increased complex-binding affinity), and does the direction of effect predict
    the clinical subphenotype (DEE versus milder intellectual disability versus
    ataxic or myasthenic features)?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#SNAP-25 SNARE Assembly Defect
  - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
  rationale: >-
    SNAP25-DEE is caused by a mix of missense and loss-of-function de novo
    variants, but structural modeling in the defining cohort could only predict
    "possible functional defects" without resolving whether release is reduced by
    haploinsufficiency or by a dominant-negative variant that is incorporated into
    the SNARE complex and poisons it. The blind-drunk mouse shows that a SNAP-25
    missense change can act paradoxically by *increasing* SNARE-complex binding
    affinity rather than abolishing it, so direction of effect cannot be assumed
    from the variant class alone. This matters therapeutically: allele-silencing
    or protein-replacement strategies help only true loss of function, whereas a
    dominant-negative allele may need selective knockdown of the mutant transcript.
  evidence:
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Structural modeling for all variants predicted possible functional defects
      concerning SNAP25 or impaired interaction with other components of the SNARE
      complex.
    explanation: >-
      Shows that the human cohort establishes disruption of SNAP-25 or its SNARE
      interactions but does not resolve the direction of effect (loss versus
      dominant-negative) for individual variants.
  - reference: PMID:17283335
    reference_title: "A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The causative I67T missense mutation results in increased binding affinities
      within the SNARE complex, impaired exocytotic vesicle recycling and granule
      exocytosis in pancreatic beta-cells, and a reduction in the amplitude of
      evoked cortical excitatory postsynaptic potentials.
    explanation: >-
      Demonstrates that a SNAP-25 missense variant can act by increasing, not
      abolishing, SNARE-complex binding affinity, showing the direction of effect
      is not predictable from variant class and motivating the gap.
  - reference: PMID:32559416
    reference_title: "SNAREopathies: Diversity in Mechanisms and Symptoms."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      We argue that disease severity generally scales with functional redundancy
    explanation: >-
      Frames the SNAREopathy expectation that mechanism and severity vary with
      redundancy, supporting the need to resolve per-variant direction of effect.
  proposed_experiments:
  - experiment_id: exp_snap25_variant_direction_release_panel
    name: SNAP25 variant direction-of-effect release panel
    description: >-
      Express representative SNAP25 DEE variants (missense and loss-of-function) in
      Snap25-null neurons alone and co-expressed with wild-type SNAP-25 in an
      isogenic background, then measure evoked release and SNARE-complex assembly
      to classify each variant as loss-of-function versus dominant-negative.
    experiment_type:
      preferred_term: variant functional-classification and rescue experiment
    perturbations:
    - name: SNAP25 variant expression on null background
      target: pathophysiology#SNAP-25 SNARE Assembly Defect
      genes:
      - preferred_term: SNAP25
        term:
          id: hgnc:11132
          label: SNAP25
      description: >-
        Introduce each DEE variant into Snap25-null neurons, with and without
        co-expressed wild-type SNAP-25, to test for haploinsufficiency versus
        dominant interference.
    readouts:
    - name: Evoked release and SNARE assembly
      target: pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
      biological_processes:
      - preferred_term: calcium-dependent activation of synaptic vesicle fusion
        term:
          id: GO:0099502
          label: calcium-dependent activation of synaptic vesicle fusion
        modifier: DECREASED
      - preferred_term: synaptic vesicle exocytosis
        term:
          id: GO:0016079
          label: synaptic vesicle exocytosis
        modifier: DECREASED
      assays:
      - preferred_term: patch-clamp electrophysiology assay
      - preferred_term: co-immunoprecipitation assay
      direction: NEGATIVE
    controls:
    - name: Wild-type SNAP-25 rescue
      description: Snap25-null neurons rescued with wild-type human SNAP-25.
    - name: Null baseline
      description: Snap25-null neurons without rescue as the loss-of-function floor.
    decision_criterion: >-
      A variant is loss-of-function if it fails to restore evoked release on the
      null background and does not depress wild-type-mediated release when
      co-expressed; it is dominant-negative if co-expression with wild-type
      SNAP-25 reduces release below the wild-type-only level.
    would_support:
    - pathophysiology#SNAP-25 SNARE Assembly Defect
    - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion

- discussion_id: gap_snap25_channel_modulation_vs_release_failure
  prompt: >-
    How much of the cortical hyperexcitability and seizure phenotype in
    SNAP25-DEE arises from impaired calcium-triggered vesicle fusion (release
    failure) versus SNAP-25's separable, non-fusion modulation of presynaptic
    voltage-gated calcium and potassium channels (a channelopathy-like change in
    intrinsic excitability)?
  kind: OPEN_QUESTION
  status: OPEN
  attaches_to:
  - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
  - pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures
  rationale: >-
    The curated causal chain routes the phenotype through reduced SNARE-mediated
    release, but SNAP-25 has well-described roles beyond exocytosis, including
    negative modulation of voltage-gated calcium channels and interactions that
    tune neuronal excitability. Because DEE variants sit in the same protein that
    performs both jobs, the seizure phenotype could reflect a release deficit, a
    channelopathy-like intrinsic-excitability shift, or both — and the balance may
    differ by variant and neuron type. Distinguishing these arms is needed before
    excitability-targeted therapy is rationalized, and it is not resolved by the
    current release-centric evidence.
  evidence:
  - reference: PMID:17283335
    reference_title: "A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The causative I67T missense mutation results in increased binding affinities
      within the SNARE complex, impaired exocytotic vesicle recycling and granule
      exocytosis in pancreatic beta-cells, and a reduction in the amplitude of
      evoked cortical excitatory postsynaptic potentials.
    explanation: >-
      Documents that a SNAP-25 variant reduces evoked cortical release (the fusion
      arm) but does not measure the channel-modulation contribution to
      excitability, leaving the relative weighting open.
  - reference: PMID:32559416
    reference_title: "SNAREopathies: Diversity in Mechanisms and Symptoms."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      subtle differences in components being rate limiting in different types of
      neurons helps to explain the main symptoms.
    explanation: >-
      Supports the expectation that SNARE-component effects are neuron-type
      dependent, consistent with a mixed release-plus-excitability contribution
      that must be disentangled.
  proposed_experiments:
  - experiment_id: exp_snap25_release_vs_intrinsic_excitability
    name: SNAP25 release versus intrinsic-excitability dissection
    description: >-
      In neurons expressing SNAP25 DEE variants, separately quantify evoked
      synaptic release and cell-autonomous intrinsic excitability (voltage-gated
      calcium and potassium current density, action-potential threshold and
      firing) to apportion the excitability change between fusion failure and
      channel modulation.
    experiment_type:
      preferred_term: electrophysiological mechanism-dissection experiment
    perturbations:
    - name: SNAP25 DEE variant expression
      target: pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
      genes:
      - preferred_term: SNAP25
        term:
          id: hgnc:11132
          label: SNAP25
      description: >-
        Express DEE variants in neurons and compare against wild-type SNAP-25 and
        null controls.
    readouts:
    - name: Evoked synaptic transmission
      target: pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
      biological_processes:
      - preferred_term: chemical synaptic transmission
        term:
          id: GO:0007268
          label: chemical synaptic transmission
        modifier: DECREASED
      assays:
      - preferred_term: patch-clamp electrophysiology assay
      direction: NEGATIVE
    - name: Intrinsic excitability and channel currents
      target: pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures
      assays:
      - preferred_term: voltage-clamp current-density assay
      - preferred_term: current-clamp firing assay
      direction: POSITIVE
    controls:
    - name: Wild-type SNAP-25
      description: Neurons expressing wild-type SNAP-25.
    - name: Snap25-null
      description: Null neurons isolating the loss-of-function reference.
    decision_criterion: >-
      The channel-modulation arm is supported if DEE variants shift intrinsic
      excitability (altered calcium or potassium current density, firing, or
      threshold) beyond what is accounted for by the measured reduction in evoked
      release; otherwise the phenotype is release-dominated.
    would_support:
    - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
    - pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

- discussion_id: gap_snap25_mouse_model_human_dee_fidelity
  prompt: >-
    Do existing Snap25 point-mutant mouse models, which reproduce ataxia,
    sensorimotor-gating deficits, and reduced cortical release, faithfully model
    the human SNAP25-DEE trajectory of before-age-two epileptic encephalopathy
    with intellectual disability, or do they capture only a partial, non-epileptic
    slice of the human phenotype?
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
  - pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures
  rationale: >-
    The strongest mechanistic in vivo evidence for SNAP-25 dysfunction comes from
    the blind-drunk I67T mouse, whose overt phenotype is ataxia and impaired
    sensorimotor gating with reduced evoked cortical release — features linked to
    psychiatric rather than epileptic disease. Human SNAP25-DEE, by contrast, is
    defined by early-onset epilepsy and intellectual disability with onset mostly
    before age two. Whether the mouse recapitulates the human epileptic
    encephalopathy trajectory, or only the synaptic and motor substrate, is the
    open translational question; this determines whether the model is a valid
    platform for testing DEE-directed therapies.
  evidence:
  - reference: PMID:17283335
    reference_title: "A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The mice also display ataxia and impaired sensorimotor gating, a phenotype
      which has been associated with psychiatric disorders in humans.
    explanation: >-
      Establishes the model-organism phenotype (ataxia, sensorimotor gating)
      whose correspondence to the human DEE trajectory is uncertain.
  - reference: PMID:33299146
    reference_title: "De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      intellectual disability and early-onset epilepsy mostly occurring before the
      age of two years.
    explanation: >-
      States the human clinical trajectory against which the mouse model's
      fidelity must be judged.
  proposed_experiments:
  - experiment_id: exp_snap25_ki_epileptogenesis_phenotyping
    name: SNAP25 patient-variant knock-in epileptogenesis phenotyping
    description: >-
      Generate knock-in mice carrying recurrent human SNAP25 DEE variants and
      phenotype for spontaneous seizures and epileptiform EEG, developmental
      cognitive assays, and cortical excitatory/inhibitory balance, comparing the
      trajectory and age of onset against the human before-age-two course.
    experiment_type:
      preferred_term: patient-variant knock-in mouse phenotyping experiment
    perturbations:
    - name: Human DEE variant knock-in
      target: pathophysiology#SNAP-25 SNARE Assembly Defect
      genes:
      - preferred_term: SNAP25
        term:
          id: hgnc:11132
          label: SNAP25
      description: >-
        Introduce a recurrent human SNAP25 DEE variant at the mouse locus.
    readouts:
    - name: Seizures and cortical excitability
      target: pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures
      biological_processes:
      - preferred_term: chemical synaptic transmission
        term:
          id: GO:0007268
          label: chemical synaptic transmission
        modifier: ABNORMAL
      assays:
      - preferred_term: video-EEG seizure monitoring
      direction: POSITIVE
    controls:
    - name: Wild-type littermates
      description: Littermate controls without the knock-in variant.
    decision_criterion: >-
      The model faithfully represents SNAP25-DEE if knock-in mice develop
      early spontaneous seizures with epileptiform EEG and developmental cognitive
      deficits on a timeline analogous to the human before-age-two onset; absence
      of an epileptic phenotype indicates a human-model mismatch limited to the
      synaptic/motor substrate.
    would_support:
    - pathophysiology#Impaired SNARE-Mediated Vesicle Fusion
    - pathophysiology#Cortical Excitation-Inhibition Imbalance and Seizures

📚

References & Deep Research

References

2

PMID:33299146

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

No top-level findings curated for this source.

PMID:32559416

SNAREopathies: Diversity in Mechanisms and Symptoms.

No top-level findings curated for this source.

SNAP25-Related Developmental and Epileptic Encephalopathy

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