Childhood-onset epilepsy syndrome

Summary

Childhood-onset epilepsy syndrome (MONDO:0020072) is a disease (an umbrella term covering 16 Mondo subtypes) with 2 cohort genes.

At a glance

• Umbrella term: 16 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood-onset epilepsy syndrome
Mondo ID	MONDO:0020072
Orphanet	98259
UMLS	C5681526
MedGen	1843031
GARD	0019437
Is cancer (heuristic)	no

Also known as: childhood epilepsy syndrome · childhood-onset epilepsy syndrome · epilepsy syndrome of childhood · paediatric epilepsy syndrome · pediatric epilepsy syndrome

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › childhood-onset epilepsy syndrome

Related subtypes (7): adolescence-adult electroclinical syndrome, benign focal seizures of adolescence, neonatal epilepsy syndrome, infantile epilepsy syndrome, neonatal/infantile epilepsy syndrome, myoclonic epilepsy, variable age epilepsy syndrome

Subtypes (16): self-limited childhood occipital epilepsy, Landau-Kleffner syndrome, rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome, perioral myoclonia with absences, cryptogenic late-onset epileptic spasms, rolandic epilepsy-speech dyspraxia syndrome, early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation, familial partial epilepsy, acute encephalopathy with biphasic seizures and late reduced diffusion, new-onset refractory status epilepticus, atypical childhood epilepsy with centrotemporal spikes, Sunflower syndrome, childhood-onset genetic generalized epilepsy syndrome, childhood-onset idiopathic generalized epilepsy syndrome, childhood-onset epilepsy syndrome with developmental and/or epileptic encephalopathy, childhood-onset self-limited focal epilepsy syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
39599	NM_020822.3(KCNT1):c.1193G>A (p.Arg398Gln)	KCNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233449	NM_001694.4(ATP6V0C):c.283G>A (p.Ala95Thr)	AMDHD2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNT1	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNT1	Orphanet:98784	Sleep-related hypermotor epilepsy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNT1	HGNC:18865	ENSG00000107147	Q5JUK3	Potassium channel subfamily T member 1	clinvar
AMDHD2	HGNC:24262	ENSG00000162066	Q9Y303	N-acetylglucosamine-6-phosphate deacetylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNT1	Potassium channel subfamily T member 1	Sodium-activated K(+) channel.
AMDHD2	N-acetylglucosamine-6-phosphate deacetylase	Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNT1	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
AMDHD2	Other/Unknown	no		GlcNAc_6-P_deAcase, Amidohydro-rel, Metal-dep_hydrolase_composite

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNT1	153	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
AMDHD2	173	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNT1	1,562
AMDHD2	1,296

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNT1	Q5JUK3	6
AMDHD2	Q9Y303	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of UDP-N-acetyl-glucosamine	1	1427.5×	0.004	AMDHD2
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.010	AMDHD2
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.010	AMDHD2
Asparagine N-linked glycosylation	1	60.1×	0.025	AMDHD2
Post-translational protein modification	1	19.2×	0.063	AMDHD2
Metabolism of proteins	1	12.4×	0.081	AMDHD2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of UDP-N-acetylglucosamine biosynthetic process	1	8426.0×	7e-04	AMDHD2
N-acetylglucosamine catabolic process	1	1685.2×	0.002	AMDHD2
N-acetylneuraminate catabolic process	1	1203.7×	0.002	AMDHD2
UDP-N-acetylglucosamine biosynthetic process	1	766.0×	0.002	AMDHD2
protein homotetramerization	1	118.7×	0.010	KCNT1
potassium ion transmembrane transport	1	68.0×	0.015	KCNT1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KCNT1	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNT1	2	4
AMDHD2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNT1	24	Binding:24
AMDHD2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNT1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AMDHD2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
AMDHD2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.