Childhood-Onset Epilepsy Syndromes

name: Childhood-Onset Epilepsy Syndromes
creation_date: "2026-07-01T00:00:00Z"
description: >-
  Childhood-onset epilepsy syndromes are epilepsy syndromes defined by their
  characteristic age at onset (the infantile-to-childhood window) under the
  ILAE age-at-onset classification framework, rather than by a shared molecular
  mechanism. Members span a broad severity and prognosis spectrum, from
  self-limited forms with normal development and spontaneous remission (benign
  familial infantile epilepsy) to developmental and epileptic encephalopathies
  with cognitive regression (Dravet syndrome; Landau-Kleffner syndrome / acquired
  epileptic aphasia). Because the ILAE syndrome framework is organized primarily
  by age at onset and electroclinical presentation, these syndromes are grouped
  by clinical convention even though their underlying mechanisms diverge
  (voltage-gated sodium channelopathy, NMDA-receptor / glutamatergic synaptic
  dysfunction, and synaptic-vesicle / membrane-excitability defects).
grouping_basis:
- CLINICAL_CONVENTION
- SHARED_PHENOTYPE
grouping_rationale: >-
  This grouping lumps by the ILAE age-at-onset syndrome convention: each member
  is a recognized epilepsy syndrome whose defining feature is childhood or
  infantile onset of seizures, and the group is assembled below the level of the
  MONDO taxonomy to make that clinical convention auditable. Members are kept as
  separate Disease entries because their causal mechanisms and prognoses diverge
  sharply — SCN1A loss-of-function Nav1.1 channelopathy in Dravet syndrome
  (developmental and epileptic encephalopathy), GRIN2A / GluN2A NMDA-receptor
  dysfunction in Landau-Kleffner syndrome (acquired epileptic aphasia with
  electrical status epilepticus in sleep), and PRRT2 synaptic dysfunction in
  benign familial infantile epilepsy (self-limited, remitting). The grouping
  basis is therefore CLINICAL_CONVENTION (ILAE age-at-onset nosology) plus the
  SHARED_PHENOTYPE of seizures, not a shared mechanism. This is deliberately
  distinct from the mechanism grouping
  Epilepsy_Excitation_Inhibition_Imbalance_Disorders, which groups entries by the
  final-common-pathway excitation/inhibition-imbalance mechanism regardless of
  onset age; the two groupings are orthogonal axes (clinical age-at-onset
  convention here vs. converging pathomechanism there) and are intentionally not
  merged or duplicated.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0020072
      label: childhood-onset epilepsy syndrome
    mapping_predicate: skos:broadMatch
    mapping_source: MONDO
    mapping_justification: >-
      MONDO:0020072 (childhood-onset epilepsy syndrome) is the umbrella MONDO
      class for epilepsy syndromes with childhood onset. This grouping is a
      curated union of three specific childhood-onset epilepsy syndrome entries
      and does not attempt to recapitulate the full MONDO subtree, so the mapping
      is asserted as broadMatch: the MONDO class subsumes many additional
      syndromes not enumerated here.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        All three members (Dravet syndrome MONDO:0100135, Landau-Kleffner
        syndrome MONDO:0009509, benign familial infantile epilepsy
        MONDO:0017615) are childhood/infantile-onset epilepsy syndromes
        consistent with the MONDO:0020072 umbrella class, though the grouping
        covers only a small subset of its descendants.
membership_criteria:
- description: >-
    A member is a recognized epilepsy syndrome (seizures are a defining feature)
    with childhood or infantile age at onset under the ILAE age-at-onset
    classification.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: HAS_PHENOTYPE
      description: Seizures are a defining feature of the syndrome.
      phenotype_term:
        preferred_term: Seizure
        term:
          id: HP:0001250
          label: Seizure
    - criterion_predicate: OTHER
      description: >-
        Childhood or infantile age at onset per the ILAE age-at-onset
        classification of epilepsy syndromes. (Onset age is not currently
        expressible as a structured leaf predicate, so it is asserted as an
        OTHER criterion; the advisory evaluator reports this leaf as UNKNOWN per
        member, which is expected.)
members:
- member: Dravet_syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Dravet syndrome is a developmental and epileptic encephalopathy caused by
      de novo heterozygous loss-of-function variants in SCN1A (Nav1.1). Reduced
      Nav1.1 function preferentially impairs GABAergic inhibitory interneurons,
      producing treatment-resistant seizures beginning in infancy with
      subsequent developmental regression — the most severe, channelopathy-driven
      end of this grouping.
    gene:
      preferred_term: SCN1A
      term:
        id: hgnc:10585
        label: SCN1A
- member: Landau-Kleffner Syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Landau-Kleffner syndrome (acquired epileptic aphasia) is characterized by
      acquired language regression and electrical status epilepticus in sleep
      (ESES/CSWS). A substantial fraction of cases are caused by GRIN2A
      variants, implicating GluN2A NMDA-receptor / glutamatergic synaptic
      dysfunction — distinct from the sodium channelopathy of Dravet and the
      synaptic PRRT2 defect of BFIE.
    gene:
      preferred_term: GRIN2A
      term:
        id: hgnc:4585
        label: GRIN2A
- member: Benign Familial Infantile Epilepsy
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Benign (self-limited) familial infantile epilepsy is an autosomal-dominant,
      self-remitting infantile seizure disorder most frequently caused by
      heterozygous loss-of-function variants in PRRT2. Seizures begin in infancy
      and remit spontaneously with normal development — the benign,
      self-limited end of the grouping's prognosis spectrum, contrasting with the
      encephalopathic members.
    gene:
      preferred_term: PRRT2
      term:
        id: hgnc:30500
        label: PRRT2
notes: >-
  Clinical-convention grouping by ILAE age at onset, kept deliberately distinct
  from the mechanism grouping Epilepsy_Excitation_Inhibition_Imbalance_Disorders.
  The NECESSARY criteria pair a Seizure phenotype leaf with an OTHER onset-age
  leaf; the advisory evaluator reports the OTHER leaf as UNKNOWN per member,
  which is expected and advisory only.