Opsoclonus-myoclonus syndrome

Summary

Opsoclonus-myoclonus syndrome (MONDO:0015247) is a disease with 2 cohort genes and 4 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous and dexamethasone acetate.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Phenotypes (HPO): 22
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.02	Europe	Validated
Annual incidence	<1 / 1 000 000	0.018	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000570	Abnormal saccadic eye movements	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0002360	Sleep abnormality	Very frequent (80-99%)
HP:0010543	Opsoclonus	Very frequent (80-99%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0002321	Vertigo	Frequent (30-79%)
HP:0002664	Neoplasm	Frequent (30-79%)
HP:0003006	Neuroblastoma	Frequent (30-79%)
HP:0045084	Limb myoclonus	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:5000002	Anti-Amphiphysin antibody	Frequent (30-79%)
HP:0001298	Encephalopathy	Occasional (5-29%)
HP:0002063	Rigidity	Occasional (5-29%)
HP:0002861	Melanoma	Occasional (5-29%)
HP:0003002	Breast carcinoma	Occasional (5-29%)
HP:0012226	Ovarian teratoma	Occasional (5-29%)
HP:0030057	Autoimmune antibody positivity	Occasional (5-29%)
HP:0030357	Small cell lung carcinoma	Occasional (5-29%)
HP:0031035	Chronic infection	Occasional (5-29%)
HP:0100526	Neoplasm of the lung	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	opsoclonus-myoclonus syndrome
Mondo ID	MONDO:0015247
EFO	EFO:1001383
MeSH	D053578
Orphanet	1183
NCIT	C4686
SNOMED CT	230350000
UMLS	C0393626
MedGen	97955
GARD	0010009
MedDRA	10053854
NORD	1527
Is cancer (heuristic)	no

Also known as: Ataxo-opso-myoclonus syndrome · dancing eye syndrome · dancing eye-dancing feet syndrome · Kinsbourne syndrome · oma syndrome · OMS · opsoclonus myoclonus syndrome · Opsoclonus-Myoclonus-Ataxia Syndrome · opsoclonus-myoclonus-ataxia syndrome · paraneoplastic opsoclonus-myoclonus · paraneoplastic opsoclonus-myoclonus-ataxia syndrome · POMA syndrome

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › opsoclonus-myoclonus syndrome

Related subtypes (53): cerebellar ataxia, chronic tic disorder, choreatic disease, extrapyramidal and movement disease, benign shuddering attacks, transient tic disorder, essential tremor, lingual-facial-buccal dyskinesia, kuru, inherited Creutzfeldt-Jakob disease, Tourette syndrome, clonic hemifacial spasm, Huntington disease, multiple system atrophy, spinal muscular atrophy-progressive myoclonic epilepsy syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, hereditary geniospasm, tremor-nystagmus-duodenal ulcer syndrome, arthrogryposis, Lafora disease, Unverricht-Lundborg syndrome, neuronal intranuclear inclusion disease, Huntington disease-like 3, brain-lung-thyroid syndrome, myoclonus, familial, proximal myopathy with extrapyramidal signs, progressive myoclonic epilepsy type 7, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, progressive non-fluent aphasia, isolated facial myokymia, primary orthostatic tremor, familial congenital mirror movements, neuroacanthocytosis, behavioral variant of frontotemporal dementia, frontotemporal dementia with motor neuron disease, hyperekplexia, intellectual disability-hyperkinetic movement-truncal ataxia syndrome, neurodegeneration with brain iron accumulation, Huntington disease-like syndrome due to C9ORF72 expansions, variably protease-sensitive prionopathy, corticobasal syndrome, sensorineural hearing loss-early graying-essential tremor syndrome, progressive supranuclear palsy, Sandifer syndrome, psychogenic movement disorders, epilepsy with myoclonic absences, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, childhood-onset benign chorea with striatal involvement, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, PRRT2-associated paroxysmal movement disorder, SLC6A3-related dopamine transporter deficiency syndrome, dyskinesia with orofacial involvement, autosomal dominant, complex movement disorder with or without neurodevelopmental features

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
371805	NM_004168.4(SDHA):c.1534C>T (p.Arg512Ter)	SDHA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1707413	NM_000336.3(SCNN1B):c.1609C>T (p.Leu537Phe)	SCNN1B	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCNN1B	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1B	Orphanet:526	Liddle syndrome
SCNN1B	Orphanet:60033	Idiopathic bronchiectasis
SDHA	Orphanet:139411	Carney triad
SDHA	Orphanet:154	Familial isolated dilated cardiomyopathy
SDHA	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHA	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHA	Orphanet:44890	Gastrointestinal stromal tumor
SDHA	Orphanet:97286	Carney-Stratakis 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
SCNN1B	HGNC:10600	ENSG00000168447	P51168	Epithelial sodium channel subunit beta	clinvar
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCNN1B	Epithelial sodium channel subunit beta	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
SDHA	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCNN1B	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd

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
esophagus mucosa	1
lower esophagus mucosa	1
rectum	1
apex of heart	1
heart left ventricle	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCNN1B	188	broad	marker	lower esophagus mucosa, esophagus mucosa, rectum
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SDHA	6,141
SCNN1B	1,013

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1B	P51168	5
SDHA	P31040	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory perception of salty taste	1	951.7×	0.012	SCNN1B
Maturation of TCA enzymes and regulation of TCA cycle	1	285.5×	0.016	SDHA
Citric acid cycle (TCA cycle)	1	211.5×	0.016	SDHA
Sensory perception of taste	1	167.9×	0.016	SCNN1B
Stimuli-sensing channels	1	68.0×	0.027	SCNN1B
Ion channel transport	1	48.0×	0.027	SCNN1B
Respiratory electron transport	1	47.6×	0.027	SDHA
Sensory Perception	1	47.6×	0.027	SCNN1B
Aerobic respiration and respiratory electron transport	1	44.3×	0.027	SDHA
Transport of small molecules	1	12.6×	0.086	SCNN1B
Metabolism	1	5.8×	0.165	SDHA

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
aldosterone metabolic process	1	4213.0×	0.003	SCNN1B
leukocyte activation involved in inflammatory response	1	2808.7×	0.003	SCNN1B
sensory perception of salty taste	1	2106.5×	0.003	SCNN1B
neutrophil-mediated killing of bacterium	1	2106.5×	0.003	SCNN1B
succinate metabolic process	1	1685.2×	0.003	SDHA
mitochondrial electron transport, succinate to ubiquinone	1	1685.2×	0.003	SDHA
cellular response to aldosterone	1	1203.7×	0.003	SCNN1B
epithelial fluid transport	1	1053.2×	0.003	SCNN1B
cellular response to vasopressin	1	1053.2×	0.003	SCNN1B
neutrophil activation involved in immune response	1	936.2×	0.003	SCNN1B
artery smooth muscle contraction	1	936.2×	0.003	SCNN1B
multicellular organismal-level water homeostasis	1	842.6×	0.003	SCNN1B
sensory perception of sour taste	1	842.6×	0.003	SCNN1B
erythrocyte homeostasis	1	648.1×	0.003	SCNN1B
mucus secretion	1	648.1×	0.003	SCNN1B
renal system process	1	561.7×	0.004	SCNN1B
sodium ion homeostasis	1	468.1×	0.004	SCNN1B
respiratory electron transport chain	1	421.3×	0.004	SDHA
intracellular sodium ion homeostasis	1	383.0×	0.004	SCNN1B
potassium ion homeostasis	1	383.0×	0.004	SCNN1B
cellular response to acidic pH	1	366.4×	0.004	SCNN1B
sodium ion import across plasma membrane	1	312.1×	0.005	SCNN1B
tricarboxylic acid cycle	1	255.3×	0.005	SDHA
response to food	1	247.8×	0.005	SCNN1B
lung alveolus development	1	175.5×	0.007	SCNN1B
proton motive force-driven mitochondrial ATP synthesis	1	131.7×	0.009	SDHA
regulation of blood pressure	1	110.9×	0.011	SCNN1B
sodium ion transmembrane transport	1	101.5×	0.011	SCNN1B
multicellular organism growth	1	68.5×	0.016	SCNN1B
gene expression	1	39.9×	0.027	SCNN1B

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Carmustine, Cytarabine, Etoposide, Melphalan, Prednisone.

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
SDHA	LINEZOLID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SDHA	1	4
SCNN1B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LINEZOLID	4	SDHA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCNN1B	5	Binding:3, ADMET:1, Functional:1
SDHA	3	Binding:3

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

1 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)
LINEZOLID	4	SDHA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SDHA
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	SCNN1B

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)
SCNN1B	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1
PHASE1/PHASE2	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01868269	PHASE3	COMPLETED	Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)
NCT00716066	PHASE2	ACTIVE_NOT_RECRUITING	Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT00806182	Not specified	COMPLETED	Study of Cytokines in Children With Opsoclonus-Myoclonus Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	1
DEXAMETHASONE ACETATE	4	1
CHEMBL63565	0	1