Myoclonus-dystonia syndrome

Summary

Myoclonus-dystonia syndrome (MONDO:0000903) is a disease with 3 cohort genes and 3 clinical trials. Top therapeutic interventions include zonisamide.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 2
• Phenotypes (HPO): 11
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001332	Dystonia	Very frequent (80-99%)
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0010531	Spinal myoclonus	Very frequent (80-99%)
HP:0045084	Limb myoclonus	Very frequent (80-99%)
HP:0000473	Torticollis	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000722	Compulsive behaviors	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0002356	Writer’s cramp	Frequent (30-79%)
HP:0012075	Personality disorder	Frequent (30-79%)
HP:0025269	Panic attack	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonus-dystonia syndrome
Mondo ID	MONDO:0000903
MeSH	C536096
Orphanet	36899
DOID	DOID:0090033
SNOMED CT	439732004
GARD	0007139
Is cancer (heuristic)	no

Also known as: alcohol-responsive dystonia · dystonia 11 · dystonia 11, myoclonic · dystonia with myoclonus · dystonia, alcohol responsive · dystonia, alcohol-responsive · dystonia-11, myoclonic · DYT-SGCE · DYT11 · Hereditary essential myoclonus · hereditary essential myoclonus · myoclonic dystonia · myoclonus, hereditary essential · myoclonus-Dystonia · myoclonus-dystonia · myoclonus-dystonia syndrome

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records · 6 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › combined dystonia › myoclonus-dystonia syndrome

Related subtypes (9): dystonia 12, X-linked dystonia-parkinsonism, dystonia 16, parkinsonism-dystonia, infantile, paroxysmal dystonia, infantile epileptic-dyskinetic encephalopathy, ataxia - telangiectasia variant, combined cervical dystonia, dystonia-aphonia syndrome

Subtypes (3): myoclonic dystonia 11, myoclonic dystonia 15, myoclonic dystonia 26

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 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
420156	NM_003919.3(SGCE):c.551T>C (p.Leu184Pro)	CASD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3068668	NM_003919.3(SGCE):c.677T>A (p.Val226Asp)	CASD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
SGCE	Definitive	Autosomal dominant	myoclonic dystonia 11	6
KCTD17	Strong	Autosomal dominant	myoclonic dystonia 26	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCE	Orphanet:36899	Myoclonus-dystonia syndrome
KCTD17	Orphanet:36899	Myoclonus-dystonia syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGCE	HGNC:10808	ENSG00000127990	O43556	Epsilon-sarcoglycan	gencc
KCTD17	HGNC:25705	ENSG00000100379	Q8N5Z5	BTB/POZ domain-containing protein KCTD17	gencc
CASD1	HGNC:16014	ENSG00000127995	Q96PB1	N-acetylneuraminate (7)9-O-acetyltransferase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCE	Epsilon-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
KCTD17	BTB/POZ domain-containing protein KCTD17	Substrate-adapter for CUL3-RING ubiquitin ligase complexes which mediates the ubiquitination and subsequent proteasomal degradation of TCHP, a protein involved in ciliogenesis down-regulation.
CASD1	N-acetylneuraminate (7)9-O-acetyltransferase	Key enzyme in the biosynthesis of O-acetylated (O-Ac) sialoglycans such as gangliosides O-AcGD3 and O-AcGD2, which affect various processes such as cell-cell interactions, host-pathogen recognition.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGCE	Other/Unknown	no		Cadg, Sarcoglycan_alpha/epsilon, Sarcoglycan_N
KCTD17	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
CASD1	Enzyme (other)	yes	2.3.1.45	Cas1_AcylTrans_dom, Cyclin-like_sf, NXPE4_C

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
right ovary	1
tendon of biceps brachii	1
caudate nucleus	1
nucleus accumbens	1
putamen	1
Ammon’s horn	1
adrenal tissue	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGCE	289	ubiquitous	marker	tendon of biceps brachii, left ovary, right ovary
KCTD17	225	ubiquitous	yes	putamen, caudate nucleus, nucleus accumbens
CASD1	278	ubiquitous	marker	adrenal tissue, postcentral gyrus, Ammon’s horn

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCTD17	1,130
SGCE	909
CASD1	426

Intra-cohort edges

A	B	Sources
CASD1	SGCE	string_interaction
KCTD17	SGCE	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCTD17	Q8N5Z5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CASD1	Q96PB1	87.87
SGCE	O43556	74.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 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
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.010	SGCE
Non-integrin membrane-ECM interactions	1	154.3×	0.010	SGCE
Extracellular matrix organization	1	63.1×	0.016	SGCE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endoplasmic reticulum calcium ion homeostasis	1	280.9×	0.016	KCTD17
positive regulation of cilium assembly	1	255.3×	0.016	KCTD17
cell projection organization	1	124.8×	0.021	KCTD17
muscle organ development	1	55.6×	0.028	SGCE
cell-matrix adhesion	1	54.5×	0.028	SGCE
carbohydrate metabolic process	1	45.3×	0.028	CASD1
protein homooligomerization	1	40.7×	0.028	KCTD17
proteasome-mediated ubiquitin-dependent protein catabolic process	1	17.4×	0.056	KCTD17

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SGCE	0	0
KCTD17	0	0
CASD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CASD1	2.3.1.45	N-acetylneuraminate 9-O-acetyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CASD1
E	Difficult family or no structure, no drug	2	SGCE, KCTD17

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SGCE	0	—
KCTD17	0	—
CASD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01806805	PHASE3	COMPLETED	Efficacy Trial of Zonisamide for Myoclonus Dystonia
NCT03428009	Not specified	RECRUITING	Dystonia Genotype-Phenotype Correlation
NCT05671068	Not specified	COMPLETED	EMOTION & COGNITION IN MYOCLONUS DYSTONIA (AGENT10-ECODYST)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ZONISAMIDE	4	1