Epilepsy Excitation-Inhibition Imbalance Disorders

name: Epilepsy Excitation-Inhibition Imbalance Disorders
display_name: Epilepsy Excitation-Inhibition Imbalance Disorders
creation_date: "2026-06-18T00:00:00Z"
description: >-
  Epilepsy excitation-inhibition imbalance disorders are entries whose
  pathophysiology converges on neuronal network hyperexcitability: ion-channel
  or synaptic dysfunction shifts excitation and inhibition toward excessive
  excitation, producing hypersynchronous neuronal firing and recurrent
  seizures. The current grouping spans the broad Epilepsy entry and two
  UNC13A-related neurodevelopmental disorders that reach the same module through
  opposite presynaptic release mechanisms.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the shared epilepsy_excitation_inhibition_imbalance module:
  members share a final common network mechanism of altered synaptic or channel
  function, excitation-inhibition imbalance, neuronal hyperexcitability, and
  seizures. The members are kept as separate Disease entries because the broad
  Epilepsy entry represents a heterogeneous clinical-mechanistic umbrella,
  whereas the UNC13A entries are molecularly defined neurodevelopmental
  disorders distinguished by direction of presynaptic release perturbation,
  inheritance, and syndromic neurodevelopmental features.
membership_criteria:
- description: >-
    A disorder belongs to this grouping if and only if it conforms to the
    epilepsy excitation-inhibition imbalance module, linking ion-channel or
    synaptic dysfunction to neuronal hyperexcitability and recurrent seizures.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: epilepsy_excitation_inhibition_imbalance
    description: >-
      Conforms to the epilepsy excitation-inhibition imbalance module.
members:
- member: Epilepsy
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Broad epilepsy mechanism entry covering heterogeneous upstream lesions
      that converge on seizure-generating network hyperexcitability, including
      synaptic, GABAergic, mTOR, neuroinflammatory, and blood-brain-barrier
      contributors rather than a single monogenic presynaptic defect.
    biological_processes:
    - preferred_term: chemical synaptic transmission
      term:
        id: GO:0007268
        label: chemical synaptic transmission
- member: UNC13A-Related Congenital NDD with Epilepsy
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Biallelic UNC13A loss-of-function decreases synaptic vesicle exocytosis
      and chemical synaptic transmission, producing congenital hypotonia,
      epileptic encephalopathy, absent speech, and profound intellectual
      disability.
    gene:
      preferred_term: UNC13A
      term:
        id: hgnc:23150
        label: UNC13A
    biological_processes:
    - preferred_term: synaptic vesicle exocytosis
      term:
        id: GO:0016079
        label: synaptic vesicle exocytosis
      modifier: DECREASED
- member: UNC13A-Related NDD with Seizures and Movement Disorder
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Heterozygous UNC13A gain-of-function or dysregulatory missense variants
      increase or dysregulate synaptic vesicle exocytosis, producing seizures
      with speech delay, tremor, dyskinesia, and variable intellectual
      disability.
    gene:
      preferred_term: UNC13A
      term:
        id: hgnc:23150
        label: UNC13A
    biological_processes:
    - preferred_term: synaptic vesicle exocytosis
      term:
        id: GO:0016079
        label: synaptic vesicle exocytosis
      modifier: INCREASED
notes: >-
  This is a mixed mechanism/phenotype grouping. It is intentionally distinct
  from a possible excitatory-synapse-scaffold grouping, which would share the
  broad Epilepsy entry and should be handled as a cross-cutting metatype case if
  added later.