Myotonic dystrophy

Summary

Myotonic dystrophy (MONDO:0016107) is a disease (an umbrella term covering 8 Mondo subtypes) with 2 cohort genes and 32 clinical trials. Top therapeutic interventions include mexiletine, prasterone, and zeleciment basivarsen.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 32

Clinical features

Epidemiology

Prevalence records

12 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	6.7	Worldwide	Validated
Point prevalence	1-9 / 100 000	8.78	Europe	Validated
Point prevalence	>1 / 1000	189	Specific population	Validated
Point prevalence	1-9 / 100 000	2.1	Italy	Validated
Point prevalence	1-9 / 100 000	5.5	Japan	Validated
Point prevalence	1-9 / 100 000	8.4	Ireland	Validated
Point prevalence	1-5 / 10 000	13.3	Croatia	Validated
Point prevalence	1-5 / 10 000	11.6	New Zealand	Validated
Point prevalence	1-5 / 10 000	20	Finland	Validated
Point prevalence	1-9 / 100 000	1.22	Norway	Validated
Point prevalence	1-5 / 10 000	10.9	Spain	Validated
Point prevalence	1-9 / 100 000	2	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	myotonic dystrophy
Mondo ID	MONDO:0016107
MeSH	D009223
OMIM	160900
Orphanet	206647
DOID	DOID:450
ICD-10-CM	G71.11
ICD-11	192087511
NCIT	C84914
SNOMED CT	240104008
UMLS	C0027126
MedGen	10239
GARD	0010419
MedDRA	10068871
Is cancer (heuristic)	no

Also known as: inherited myotonic dystrophy · myotonia atrophica · myotonia dystrophica

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › myotonic dystrophy

Related subtypes (12): facioscapulohumeral muscular dystrophy, congenital fibrosis of extraocular muscles, Bethlem myopathy, oculopharyngeal muscular dystrophy, X-linked myopathy with excessive autophagy, myopathy, myofibrillar, 9, with early respiratory failure, progressive scapulohumeroperoneal distal myopathy, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome, oculopharyngodistal myopathy

Subtypes (8): myotonic cataract, myotonic dystrophy type 1, myotonic dystrophy type 2, congenital myotonic dystrophy, childhood-onset Steinert myotonic dystrophy, juvenile-onset Steinert myotonic dystrophy, adult-onset Steinert myotonic dystrophy, late-onset Steinert myotonic dystrophy

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
548605	NM_004409.5(DMPK):c.1697C>T (p.Pro566Leu)	DM1-AS	Uncertain significance	criteria provided, multiple submitters, no conflicts
496654	NM_004409.5(DMPK):c.643G>A (p.Gly215Ser)	DMPK	Uncertain significance	criteria provided, single submitter
496650	NM_004409.5(DMPK):c.1477C>T (p.Arg493Cys)	DM1-AS	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMPK	Orphanet:589821	Congenital-onset Steinert myotonic dystrophy
DMPK	Orphanet:589824	Childhood-onset Steinert myotonic dystrophy
DMPK	Orphanet:589827	Juvenile-onset Steinert myotonic dystrophy
DMPK	Orphanet:589830	Adult-onset Steinert myotonic dystrophy
DMPK	Orphanet:589833	Late-onset Steinert myotonic dystrophy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DMPK	HGNC:2933	ENSG00000104936	Q09013	Myotonin-protein kinase	clinvar
DM1-AS	HGNC:53125	ENSG00000267395		DM1 locus antisense RNA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DMPK	Myotonin-protein kinase	Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function.

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMPK	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
DM1-AS	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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
apex of heart	1
mucosa of stomach	1
right coronary artery	1
left ovary	1
right lobe of thyroid gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMPK	246	broad	marker	apex of heart, right coronary artery, mucosa of stomach
DM1-AS	157	broad	yes	right uterine tube, left ovary, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DMPK	2,467
DM1-AS	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DMPK	Q09013	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Ion homeostasis	1	203.9×	0.005	DMPK

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction	1	16852.0×	4e-04	DMPK
muscle cell apoptotic process	1	8426.0×	4e-04	DMPK
regulation of skeletal muscle contraction by calcium ion signaling	1	8426.0×	4e-04	DMPK
regulation of synapse structural plasticity	1	4213.0×	6e-04	DMPK
regulation of myotube differentiation	1	3370.4×	6e-04	DMPK
nuclear envelope organization	1	991.3×	0.002	DMPK
regulation of sodium ion transport	1	936.2×	0.002	DMPK
regulation of heart contraction	1	495.6×	0.003	DMPK
intracellular calcium ion homeostasis	1	145.3×	0.008	DMPK
protein phosphorylation	1	68.0×	0.015	DMPK

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Mexiletine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Mecasermin Rinfabate, Prasterone.

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
DMPK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DMPK	20	4
DM1-AS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	DMPK
RUXOLITINIB	4	DMPK
TOFACITINIB CITRATE	4	DMPK
TOFACITINIB	4	DMPK
BOSUTINIB	4	DMPK
DASATINIB	4	DMPK
ERLOTINIB	4	DMPK
CRIZOTINIB	4	DMPK
MIDOSTAURIN	4	DMPK
GEFITINIB	4	DMPK
ENZASTAURIN	3	DMPK
CANERTINIB	3	DMPK
ALVOCIDIB	3	DMPK
LESTAURTINIB	3	DMPK
RUBOXISTAURIN	3	DMPK
RG-547	2	DMPK
AT-7519	2	DMPK
BI-2536	2	DMPK
PELITINIB	2	DMPK
KW-2449	1	DMPK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DMPK	210	Binding:210

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DMPK	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DMPK	210

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

20 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)
FEDRATINIB	4	DMPK
RUXOLITINIB	4	DMPK
TOFACITINIB CITRATE	4	DMPK
TOFACITINIB	4	DMPK
BOSUTINIB	4	DMPK
DASATINIB	4	DMPK
ERLOTINIB	4	DMPK
CRIZOTINIB	4	DMPK
MIDOSTAURIN	4	DMPK
GEFITINIB	4	DMPK
ENZASTAURIN	3	DMPK
CANERTINIB	3	DMPK
ALVOCIDIB	3	DMPK
LESTAURTINIB	3	DMPK
RUBOXISTAURIN	3	DMPK
RG-547	2	DMPK
AT-7519	2	DMPK
BI-2536	2	DMPK
PELITINIB	2	DMPK
KW-2449	1	DMPK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DMPK
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	DM1-AS

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)
DM1-AS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 32.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE3	7
PHASE1/PHASE2	3
PHASE2	2
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06411288	PHASE3	ACTIVE_NOT_RECRUITING	Global Study of Del-desiran for the Treatment of DM1
NCT06523400	PHASE3	RECRUITING	The Efficacy and Safety of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2
NCT06549400	PHASE3	ENROLLING_BY_INVITATION	An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2 Who Have Completed MEX-DM-302 Study.
NCT07008469	PHASE3	ENROLLING_BY_INVITATION	Global Open-Label Extension Study of Del-desiran for the Treatment of DM1
NCT07486934	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Basivarsen (DYNE-101) in Participants With Myotonic Dystrophy Type 1
NCT00167609	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of DHEA for Myotonic Dystrophy
NCT04624750	PHASE3	COMPLETED	Open Label Study in Adolescents and Children With Myotonic Disorders
NCT04700046	PHASE3	WITHDRAWN	Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2
NCT06844214	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety, Tolerability, and Efficacy of SAR446268, an Adeno-associated Viral Vector-mediated Gene Therapy in Participants Aged 10 to 55 Years of Age With Non-congenital Myotonic Dystrophy Type 1
NCT00233519	PHASE1/PHASE2	COMPLETED	Effects of SomatoKine (Iplex)Recombinant Human Insulin-like Growth Factor-1/Recombinant Human Insulin-like Growth Factor-binding Protein-3 (rhIGF-I/rhIGFBP-3) in Myotonic Dystrophy Type 1 (DM1)
NCT01406873	PHASE2	COMPLETED	Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
NCT05027269	PHASE1/PHASE2	COMPLETED	Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT03959189	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
NCT02398786	Not specified	RECRUITING	Myotonic Dystrophy Family Registry
NCT04003363	Not specified	RECRUITING	The United Kingdom National Registry for Myotonic Dystrophy
NCT04616807	Not specified	ACTIVE_NOT_RECRUITING	An Observational Study in Adult Patients With Non-dystrophic Myotonic Disorders
NCT05019625	Not specified	RECRUITING	Biomarker Development for Muscular Dystrophies
NCT05020002	Not specified	RECRUITING	Extracellular RNA Biomarkers of Myotonic Dystrophy
NCT06147414	Not specified	RECRUITING	Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
NCT06605612	Not specified	ENROLLING_BY_INVITATION	Development and Validation of the FBIndex to Determine the Risk of Falls for Patients With Neuromuscular Disorders
NCT06747884	Not specified	RECRUITING	Trial Readiness and Endpoint Assessment in Pediatric Myotonic Dystrophy Extension
NCT07321977	Not specified	RECRUITING	Assessment of a Portable Digital Device for Quantified Analysis of Markerless Walking in Volunteers With Neuromuscular Diseases or Asymptomatic Volunteers
NCT07362875	Not specified	RECRUITING	Development of Quantitative Muscle Imaging as a Biomarker of Disease Endpoints in Myotonic Dystrophy
NCT00127582	Not specified	COMPLETED	RAMYD Study - Evaluation of Arrhythmic Risk in Myotonic Dystrophy
NCT01136330	Not specified	COMPLETED	DM1 Heart Registry - DM1 Respiratory Registry
NCT01242007	Not specified	COMPLETED	Postural Spirometry Changes in Ambulatory Myotonic Dystrophy Patients
NCT01931644	Not specified	COMPLETED	At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
NCT02315339	Not specified	TERMINATED	European Home Mechanical Ventilation Registry
NCT02375087	Not specified	COMPLETED	Sleep Breathing Disorders, a Main Trigger for Cardiac ARythmias in Type I Myotonic Dystrophy ?
NCT05890833	Not specified	COMPLETED	The Risk of Falls Index for Patients With Neuromuscular Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MEXILETINE	4	4
PRASTERONE	4	1
ZELECIMENT BASIVARSEN	2	1
CHEMBL31399	0	1