Pediatric epilepsy coverage gaps in dismech (2026-07-17)
A survey of childhood-relevant epilepsy syndromes and developmental &
epileptic encephalopathies (DEEs) that do not yet have a dedicated
Disease entry in kb/disorders/. Presence was tested against each entry's
own top-level name: field (not incidental text mentions), since many of the
genes below appear only as differential-diagnosis mentions inside unrelated
entries (e.g. Lennox-Gastaut named inside KBG_Syndrome/DNM1_Encephalopathy,
CDKL5 inside STXBP1_Encephalopathy, SCN2A/SCN8A as comparisons).
This report is the motivating analysis behind the Lennox-Gastaut syndrome curation and is a candidate worklist for subsequent pediatric-epilepsy curation batches.
Already represented (for reference)
Dravet, GEFS+, Infantile Spasms (West), GLUT1 Deficiency Syndrome, STXBP1, SNAP25, STX1B, CPLX1-DEE, DNM1, UNC13A (×2), Rett, MECP2 duplication, FOXG1, Angelman, Tuberous Sclerosis Complex, Aicardi, Jeavons, Landau-Kleffner, Pallister-Hall (gelastic/hypothalamic hamartoma), the lissencephaly spectrum (ARX, Miller-Dieker, Reelin, etc.), Menkes, Wolf-Hirschhorn, Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis, Progressive Myoclonus Epilepsy, Benign Familial Infantile Epilepsy, Benign Neonatal Seizures (KCNQ2/3 benign).
Missing — the common, high-impact childhood syndromes
- Lennox-Gastaut syndrome — defining childhood epileptic encephalopathy (tonic seizures, slow spike-wave, cognitive regression). (now in progress)
- CDKL5 deficiency disorder — one of the commonest single-gene DEEs.
- PCDH19 clustering epilepsy (girls-clustering / EFMR) — X-linked, female-predominant, cellular-interference mechanism.
- SYNGAP1-related DEE — among the commonest genetic NDD-plus-epilepsy disorders (myoclonic-atonic/absence, eyelid myoclonia).
- Childhood absence epilepsy and juvenile myoclonic epilepsy — the two
commonest genetic generalized epilepsies; currently only list-items inside the
umbrella
Epilepsy.yaml. - Self-limited epilepsy with centrotemporal spikes (SeLECTS / Rolandic / BECTS) — the single most common focal epilepsy of childhood.
Missing — high-value because treatable or mechanistically distinct
- Pyridoxine-dependent epilepsy (ALDH7A1/antiquitin) and PNPO deficiency — the archetypal vitamin-responsive neonatal epilepsies.
- KCNQ2 developmental & epileptic encephalopathy — the severe-end companion to the already-curated Benign Neonatal Seizures entry (same gene, opposite severity; directly answers a knowledge gap posed in that entry).
- Sturge-Weber syndrome — structural childhood epilepsy with a somatic-GNAQ vascular mechanism.
- Rasmussen encephalitis — immune/inflammatory unihemispheric pediatric focal epilepsy; mechanistically unlike the rest of the pool.
Missing — other recurrent DEE genes / syndromes
- Ohtahara / early-infantile DEE (neonatal anchor of the age spectrum)
- Epilepsy of infancy with migrating focal seizures (EIMFS, KCNT1)
- SCN2A-DEE, SCN8A-DEE
- Doose syndrome (epilepsy with myoclonic-atonic seizures)
- GRIN2A / GRIN2B, GNAO1, SLC6A1, CHD2, KCNB1, SLC13A5
Missing — structural / etiologic
- Hemimegalencephaly (currently only inside
CLOVES_Syndrome) - Hypothalamic hamartoma / gelastic epilepsy (currently only inside
Pallister-Hall_Syndrome) - Focal cortical dysplasia (no standalone mechanism entry)
- Panayiotopoulos syndrome, Ring chromosome 20 syndrome, Alpers syndrome (POLG)
Suggested next batches
- Treatable/companion trio: KCNQ2-DEE + pyridoxine-dependent epilepsy + PNPO deficiency.
- Commonest missing childhood DEEs: Lennox-Gastaut (in progress) + CDKL5 + PCDH19 + SYNGAP1.