Rolandic epilepsy-speech dyspraxia syndrome

Summary

Rolandic epilepsy-speech dyspraxia syndrome (MONDO:0015587) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 18

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		277	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0011098	Speech apraxia	Very frequent (80-99%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0002307	Drooling	Frequent (30-79%)
HP:0007334	Bilateral tonic-clonic seizure with focal onset	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0011196	EEG with focal sharp waves	Frequent (30-79%)
HP:0011198	EEG with generalized epileptiform discharges	Frequent (30-79%)
HP:0031491	Continuous spike and waves during slow sleep	Frequent (30-79%)
HP:0000736	Short attention span	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001611	Hypernasal speech	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002546	Incomprehensible speech	Occasional (5-29%)
HP:0010300	Abnormally low-pitched voice	Occasional (5-29%)
HP:0031434	Abnormal speech prosody	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	rolandic epilepsy-speech dyspraxia syndrome
Mondo ID	MONDO:0015587
Orphanet	163721
ICD-11	288052868
UMLS	C4707308
MedGen	1633042
GARD	0017002
Is cancer (heuristic)	no

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 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 › rolandic epilepsy-speech dyspraxia syndrome

Related subtypes (15): 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, 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

Subtypes (2): rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked, GRIN2A-related rolandic epilepsy-speech dyspraxia 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GRIN2A	Supportive	Autosomal dominant	rolandic epilepsy-speech dyspraxia syndrome	12
SRPX2	Supportive	Autosomal dominant	rolandic epilepsy-speech dyspraxia syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRPX2	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
SRPX2	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
SRPX2	Orphanet:98889	Bilateral perisylvian polymicrogyria
GRIN2A	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
GRIN2A	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GRIN2A	Orphanet:289266	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation
GRIN2A	Orphanet:725	Developmental and epileptic encephalopathy with spike-wave activation in sleep
GRIN2A	Orphanet:98818	Landau-Kleffner syndrome

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
SRPX2	HGNC:30668	ENSG00000102359	O60687	Sushi repeat-containing protein SRPX2	gencc
GRIN2A	HGNC:4585	ENSG00000183454	Q12879	Glutamate receptor ionotropic, NMDA 2A	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRPX2	Sushi repeat-containing protein SRPX2	Acts as a ligand for the urokinase plasminogen activator surface receptor.
GRIN2A	Glutamate receptor ionotropic, NMDA 2A	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).

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
Complement	1	134.0×	0.015
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRPX2	Complement	yes		Sushi_SCR_CCP_dom, HYR_dom, DUF4174
GRIN2A	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt

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
calcaneal tendon	1
cartilage tissue	1
stromal cell of endometrium	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRPX2	211	ubiquitous	marker	stromal cell of endometrium, calcaneal tendon, cartilage tissue
GRIN2A	199	broad	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRIN2A	3,146
SRPX2	954

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRIN2A	Q12879	37

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SRPX2	O60687	86.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
MECP2 regulates neuronal receptors and channels	1	601.0×	0.003	GRIN2A
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.003	GRIN2A
Synaptic adhesion-like molecules	1	543.8×	0.003	GRIN2A
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.003	GRIN2A
Long-term potentiation	1	475.8×	0.003	GRIN2A
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.005	GRIN2A
Neurexins and neuroligins	1	196.9×	0.005	GRIN2A

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
directional locomotion	1	2808.7×	0.007	GRIN2A
protein localization to postsynaptic membrane	1	2808.7×	0.007	GRIN2A
regulation of phosphorylation	1	1404.3×	0.007	SRPX2
sleep	1	1203.7×	0.007	GRIN2A
regulation of monoatomic cation transmembrane transport	1	1053.2×	0.007	GRIN2A
serotonin metabolic process	1	842.6×	0.007	GRIN2A
calcium ion transmembrane import into cytosol	1	766.0×	0.007	GRIN2A
ionotropic glutamate receptor signaling pathway	1	648.1×	0.007	GRIN2A
excitatory chemical synaptic transmission	1	648.1×	0.007	GRIN2A
startle response	1	561.7×	0.007	GRIN2A
dopamine metabolic process	1	495.6×	0.007	GRIN2A
glutamate receptor signaling pathway	1	468.1×	0.007	GRIN2A
vocalization behavior	1	443.5×	0.007	SRPX2
positive regulation of cell migration involved in sprouting angiogenesis	1	366.4×	0.008	SRPX2
regulation of neuronal synaptic plasticity	1	337.0×	0.008	GRIN2A
positive regulation of synaptic transmission, glutamatergic	1	312.1×	0.008	GRIN2A
monoatomic cation transmembrane transport	1	312.1×	0.008	GRIN2A
positive regulation of excitatory postsynaptic potential	1	263.3×	0.009	GRIN2A
response to amphetamine	1	247.8×	0.009	GRIN2A
excitatory postsynaptic potential	1	221.7×	0.009	GRIN2A
cell motility	1	200.6×	0.010	SRPX2
sensory perception of pain	1	187.2×	0.010	GRIN2A
negative regulation of protein catabolic process	1	183.2×	0.010	GRIN2A
synaptic transmission, glutamatergic	1	179.3×	0.010	GRIN2A
visual learning	1	153.2×	0.011	GRIN2A
long-term synaptic potentiation	1	140.4×	0.011	GRIN2A
regulation of synaptic plasticity	1	129.6×	0.012	GRIN2A
positive regulation of synapse assembly	1	122.1×	0.012	SRPX2
learning or memory	1	120.4×	0.012	GRIN2A
protein catabolic process	1	118.7×	0.012	GRIN2A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
GRIN2A	MEMANTINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIN2A	37	4
SRPX2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEMANTINE HYDROCHLORIDE	4	GRIN2A
ESKETAMINE	4	GRIN2A
DEXTROMETHORPHAN	4	GRIN2A
PENTAMIDINE	4	GRIN2A
AMANTADINE	4	GRIN2A
KETAMINE	4	GRIN2A
CYCLOSERINE	4	GRIN2A
MEMANTINE	4	GRIN2A
TACRINE	4	GRIN2A
LEVORPHANOL	4	GRIN2A
CHLORPROMAZINE	4	GRIN2A
PROCYCLIDINE	4	GRIN2A
ORPHENADRINE	4	GRIN2A
ESMETHADONE	3	GRIN2A
DALZANEMDOR	3	GRIN2A
LATREPIRDINE	3	GRIN2A
GLUTAMIC ACID	3	GRIN2A
DEXOXADROL	2	GRIN2A
DEXTRORPHAN	2	GRIN2A
LEVOMETHADONE	2	GRIN2A
ALPHAMETHADOL	2	GRIN2A
BETAMETHADOL	2	GRIN2A
DIMEMORFAN	2	GRIN2A
PHENCYCLIDINE	2	GRIN2A
DIZOCILPINE	2	GRIN2A
ETOXADROL	2	GRIN2A
IFENPRODIL	2	GRIN2A
TEZAMPANEL ANHYDROUS	2	GRIN2A
TRAXOPRODIL	2	GRIN2A
RADIPRODIL	2	GRIN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRIN2A	324	Binding:296, Functional:23, ADMET:4, Toxicity:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GRIN2A	324

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

30 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)
MEMANTINE HYDROCHLORIDE	4	GRIN2A
ESKETAMINE	4	GRIN2A
DEXTROMETHORPHAN	4	GRIN2A
PENTAMIDINE	4	GRIN2A
AMANTADINE	4	GRIN2A
KETAMINE	4	GRIN2A
CYCLOSERINE	4	GRIN2A
MEMANTINE	4	GRIN2A
TACRINE	4	GRIN2A
LEVORPHANOL	4	GRIN2A
CHLORPROMAZINE	4	GRIN2A
PROCYCLIDINE	4	GRIN2A
ORPHENADRINE	4	GRIN2A
ESMETHADONE	3	GRIN2A
DALZANEMDOR	3	GRIN2A
LATREPIRDINE	3	GRIN2A
GLUTAMIC ACID	3	GRIN2A
DEXOXADROL	2	GRIN2A
DEXTRORPHAN	2	GRIN2A
LEVOMETHADONE	2	GRIN2A
ALPHAMETHADOL	2	GRIN2A
BETAMETHADOL	2	GRIN2A
DIMEMORFAN	2	GRIN2A
PHENCYCLIDINE	2	GRIN2A
DIZOCILPINE	2	GRIN2A
ETOXADROL	2	GRIN2A
IFENPRODIL	2	GRIN2A
TEZAMPANEL ANHYDROUS	2	GRIN2A
TRAXOPRODIL	2	GRIN2A
RADIPRODIL	2	GRIN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRIN2A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SRPX2
E	Difficult family or no structure, no drug	0

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)
SRPX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.