🔗

Mappings

MONDO

MONDO:0008056 myotonic dystrophy type 1

Orphanet lists MONDO:0008056 as an exact cross-reference for Steinert myotonic dystrophy / myotonic dystrophy type 1.

📘

Definitions

1

Orphanet disease definition

Orphanet defines Steinert myotonic dystrophy / DM1 as a rare genetic multisystem disorder with muscle manifestations, early-onset cataracts, and cerebral, endocrine, cardiac, gastrointestinal, uterine, skin, and immunologic involvement across a broad onset spectrum.

CASE_DEFINITION

Show evidence (1 reference)

ORPHA:273 SUPPORT Other

"A rare genetic multi-system disorder characterized by a wide range of muscle-related manifestations (muscle weakness, myotonia, early onset cataracts (before age 50) and systemic manifestations (cerebral, endocrine, cardiac, gastrointestinal tract, uterus, skin and immunologic involvement) that..."

Orphanet's definition supports the multisystem clinical framing of DM1 in this entry.

👪

Inheritance

1

Autosomal dominant inheritance HP:0000006

DM1 follows autosomal dominant inheritance.

Autosomal dominant inheritance

Show evidence (1 reference)

ORPHA:273 SUPPORT Other

"Autosomal dominant"

Orphanet records autosomal dominant inheritance for Steinert myotonic dystrophy / DM1.

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Pathophysiology

10

DMPK CTG Repeat Expansion

DM1 begins with an unstable CTG trinucleotide repeat expansion in the 3'-untranslated region of DMPK. The repeat-expansion allele is germline, autosomal dominant, and becomes more unstable across generations and across tissues, providing the initiating mutation for downstream RNA toxicity.

DMPK

skeletal muscle tissue link

Downstream

Toxic CUG RNA Nuclear Foci The expanded DMPK allele is transcribed into CUG repeat-containing RNA that accumulates in nuclear foci.

SIX5/DMPK Locus Effects in Lens The repeat expansion sits adjacent to SIX5, supporting a parallel locus-dosage branch for cataract susceptibility.

Show evidence (2 references)

PMID:31326502 SUPPORT Human Clinical

"Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene."

Establishes the causal repeat expansion and anticipation.

PMID:15065017 SUPPORT Other

"In 1992, the mutation responsible for DM1 was identified as a CTG expansion located in the 3' untranslated region of the dystrophia myotonica-protein kinase gene (DMPK)."

Review-level evidence confirms the initiating DMPK 3'-UTR CTG expansion.

Toxic CUG RNA Nuclear Foci

The expanded DMPK repeat is transcribed into CUG repeat-containing RNA that forms nuclear foci. These foci are the central toxic RNA species in DM1, retaining mutant RNA in the nucleus and recruiting RNA-binding proteins that normally regulate adult splicing programs.

skeletal muscle cell link cardiac muscle cell link neuron link

RNA splicing link

nucleus link

Downstream

Splicing Factor Imbalance and Fetal Spliceopathy Expanded CUG RNA foci sequester MBNL proteins and shift CELF1/MBNL balance, producing widespread developmental splice reversion.

Show evidence (2 references)

PMID:12351998 SUPPORT Human Clinical

"In both types of myotonic dystrophy the expanded repeat is transcribed and the RNA produced from the mutant allele is retained in nuclear inclusions. Recent studies suggest that the mutant RNA has a toxic effect on muscle fibers by interfering with the essential functions of the myonucleus, such..."

Confirms the toxic RNA gain-of-function mechanism in myotonic dystrophy.

PMID:15065017 SUPPORT Other

"the clinical features common to both diseases are caused by a gain-of-function RNA mechanism in which the CUG and CCUG repeats alter cellular function, including alternative splicing of various genes."

Supports the toxic RNA gain-of-function mechanism and its connection to altered splicing.

Splicing Factor Imbalance and Fetal Spliceopathy

Expanded CUG RNA sequesters MBNL family proteins in nuclear foci and is accompanied by increased CELF1/CUGBP1 activity in affected tissues. The resulting loss of adult MBNL activity and CELF1/MBNL imbalance causes fetal-pattern alternative splicing across skeletal muscle, heart, endocrine, and CNS transcripts.

skeletal muscle cell link cardiac muscle cell link neuron link

RNA splicing link

nucleus link

Downstream

CLCN1 Mis-splicing and Reduced Chloride Conductance MBNL1 depletion causes CLCN1 mis-splicing, loss of functional ClC-1 chloride channel, and skeletal muscle hyperexcitability.

CACNA1S Mis-splicing and Excitation-Contraction Coupling Defect Mis-splicing of CaV1.1/CACNA1S alters excitation-contraction coupling in skeletal muscle and contributes to weakness.

Dysphagia Oropharyngeal skeletal muscle spliceopathy contributes to swallowing dysfunction in DM1.

INSR Splicing Shift and Insulin Resistance Aberrant insulin receptor splicing favors the lower-signaling IR-A isoform in skeletal muscle.

SCN5A Splicing Shift and Cardiac Excitability Loss Cardiac spliceopathy shifts SCN5A toward a fetal exon 6A isoform with reduced excitability.

CNS Spliceopathy and Tau Dysregulation MBNL1/2 sequestration in the CNS alters brain splicing programs, including MAPT/tau-related transcripts.

Show evidence (2 references)

PMID:18974556 SUPPORT Human Clinical

"Mutant RNA sequesters MBNL1, a splice regulator protein and depletes MBNL1 from the nucleoplasm. Loss of MBNL1 results in altered splicing of ClC-1 mRNA."

Describes the MBNL1 depletion mechanism that drives DM1 spliceopathy.

PMID:27063795 SUPPORT Human Clinical

"The pathogenesis of DM involves a RNA gain-of-function mechanism caused by expression of mutant RNAs containing hundred to thousands of CUG or CCUG repeats that interfere with the splicing of other pre-mRNAs through dysfunction of two classes of RNA-binding proteins."

Supports the broader spliceopathy mechanism downstream of expanded repeat RNA.

CLCN1 Mis-splicing and Reduced Chloride Conductance

MBNL1 sequestration causes mis-splicing of the chloride channel gene CLCN1, leading to loss of functional ClC-1 chloride channels in skeletal muscle membranes. Reduced chloride conductance causes membrane hyperexcitability and myotonia.

skeletal muscle cell link

RNA splicing link

skeletal muscle tissue link

Downstream

Myotonia Loss of functional ClC-1 chloride conductance causes the muscle hyperexcitability phenotype.

Show evidence (1 reference)

PMID:18974556 SUPPORT Human Clinical

"Altered splice products do not encode functional ClC-1 protein. Subsequent loss of chloride conductance in muscle membrane causes myotonia in the myotonic dystrophies."

Directly links CLCN1 mis-splicing to reduced chloride conductance and myotonia.

CACNA1S Mis-splicing and Excitation-Contraction Coupling Defect

DM1 spliceopathy represses inclusion of CACNA1S/CaV1.1 exon 29 in skeletal muscle. CaV1.1 controls excitation-contraction coupling, so this splice shift changes calcium-channel gating and contributes to progressive muscle weakness and myopathic changes.

skeletal muscle cell link

RNA splicing link

skeletal muscle tissue link

Downstream

Progressive Muscle Weakness Altered CaV1.1 gating impairs excitation-contraction coupling and contributes to progressive skeletal muscle weakness.

Fatigue Excitation-contraction coupling defects and myopathic changes can contribute to fatigue in DM1.

Respiratory Muscle and Central Drive Dysfunction The same skeletal muscle weakness branch can involve respiratory muscles and worsen ventilatory capacity.

Show evidence (1 reference)

PMID:22140091 SUPPORT Human Clinical

"The extent of E29 skipping correlated with severity of weakness in tibialis anterior muscle of DM1 patients."

Human muscle data link CACNA1S exon 29 skipping to weakness severity.

INSR Splicing Shift and Insulin Resistance

Aberrant splicing of insulin receptor pre-mRNA in DM1 skeletal muscle favors the lower-signaling IR-A isoform, reducing metabolic insulin responsiveness and contributing to insulin resistance and diabetes mellitus.

skeletal muscle cell link

RNA splicing link

skeletal muscle tissue link

Downstream

Insulin Resistance and Diabetes Predominant IR-A expression lowers insulin signaling in skeletal muscle and contributes to glucose intolerance and diabetes.

Show evidence (1 reference)

PMID:11528389 SUPPORT Human Clinical

"alternative splicing of the insulin receptor (IR) pre-mRNA is aberrantly regulated in DM1 skeletal muscle tissue, resulting in predominant expression of the lower-signaling nonmuscle isoform (IR-A)."

Directly supports the INSR splice shift that produces an insulin-resistant skeletal muscle phenotype.

SCN5A Splicing Shift and Cardiac Excitability Loss

In DM1 heart tissue, MBNL-dependent spliceopathy shifts SCN5A from the adult exon 6B isoform toward the fetal exon 6A isoform. The resulting Nav1.5 channel has reduced excitability, providing a mutation-to-cardiac conduction defect branch in the pathograph.

cardiac muscle cell link

RNA splicing link

heart link

Downstream

Cardiac Conduction Defects Reduced excitability of the fetal SCN5A/Nav1.5 isoform contributes to conduction delay and arrhythmia.

Show evidence (1 reference)

PMID:27063795 SUPPORT Human Clinical

"Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A."

Human heart RNA-seq identifies the SCN5A splice shift.

CNS Spliceopathy and Tau Dysregulation

DM1 affects the central nervous system through MBNL1/2 sequestration and aberrant brain splicing. MAPT/tau transcript dysregulation and abnormal tau deposition provide a mechanistic bridge to cognitive and behavioral impairment.

neuron link

RNA splicing link

brain link

Downstream

Cognitive Impairment CNS spliceopathy and tau dysregulation provide a mechanistic basis for cognitive impairment in DM1.

Excessive Daytime Somnolence CNS MBNL sequestration and aberrant brain splicing contribute to hypersomnia in DM1.

Insomnia CNS MBNL sequestration and disrupted sleep-wake circuitry contribute to sleep fragmentation and insomnia in DM1.

Show evidence (2 references)

PMID:32407311 SUPPORT Human Clinical

"This leads to the sequestration of splicing factors such as muscleblind-like 1/2 (MBNL1/2) and aberrant splicing in the central nervous system."

Human brain study supports CNS MBNL sequestration and aberrant splicing.

PMID:36331500 SUPPORT Human Clinical

"Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau protein in the CNS."

Human neuropathology links MAPT spliceopathy and CNS tau deposition.

SIX5/DMPK Locus Effects in Lens

The DM1 CTG repeat lies near SIX5, and repeat-associated local chromatin or transcriptional effects can reduce SIX5 dosage. Mouse Six5 loss produces progressive ocular cataracts, supporting a parallel lens branch in addition to toxic RNA spliceopathy.

Downstream

Cataracts DMPK/SIX5 locus effects provide a mutation-to-lens opacity path.

Show evidence (1 reference)

PMID:10802668 SUPPORT Model Organism

"Our results demonstrate that the rate and severity of cataract formation is inversely related to Six5 dosage and is temporally progressive."

Six5 dosage model supports a cataract mechanism connected to the DMPK/SIX5 locus.

Respiratory Muscle and Central Drive Dysfunction

Respiratory morbidity in DM1 reflects both peripheral respiratory muscle weakness and central respiratory drive involvement. The result is commonly restrictive ventilatory dysfunction with alveolar hypoventilation, chronic hypercapnia, and sleep-disordered breathing.

skeletal muscle cell link

Downstream

Respiratory Insufficiency Restrictive ventilatory impairment and hypoventilation manifest clinically as respiratory insufficiency.

Show evidence (1 reference)

PMID:30765255 SUPPORT Human Clinical

"respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing;"

Systematic review supports respiratory dysfunction and its major physiologic components in DM1.

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

11

Cardiovascular 1

Cardiac Conduction Defects VERY_FREQUENT Cardiac conduction abnormality (HP:0031546)

Show evidence (2 references)

PMID:27063795 SUPPORT Human Clinical

"Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM."

Supports conduction delay and arrhythmia as major cardiac manifestations of myotonic dystrophy.

ORPHA:273 SUPPORT Other

"HP:0031546 | Cardiac conduction abnormality | Very frequent (99-80%)"

Orphanet records cardiac conduction abnormality as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

Digestive 1

Dysphagia FREQUENT Dysphagia (HP:0002015)

Show evidence (1 reference)

PMID:38454488 SUPPORT Human Clinical

"Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."

Directly supports dysphagia as a frequent clinical manifestation in DM1.

Endocrine 1

Insulin Resistance and Diabetes OCCASIONAL Diabetes mellitus (HP:0000819)

Show evidence (2 references)

PMID:11528389 SUPPORT Human Clinical

"People with DM1 have an unusual form of insulin resistance caused by a defect in skeletal muscle."

Supports the insulin resistance branch that contributes to the diabetes phenotype in DM1.

ORPHA:273 SUPPORT Other

"HP:0000819 | Diabetes mellitus | Occasional (29-5%)"

Orphanet records diabetes mellitus as an occasional HPO phenotype for Steinert myotonic dystrophy / DM1.

Musculoskeletal 1

Progressive Muscle Weakness VERY_FREQUENT Muscle weakness (HP:0001324)

Course: PROGRESSIVE

Show evidence (3 references)

PMID:28780071 SUPPORT Human Clinical

"Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene."

DM1 is a neuromuscular disorder with progressive weakness as a core feature.

PMID:22140091 SUPPORT Human Clinical

"The extent of E29 skipping correlated with severity of weakness in tibialis anterior muscle of DM1 patients."

Provides a direct molecular correlation between CaV1.1 mis-splicing and weakness severity.

ORPHA:273 SUPPORT Other

"HP:0002460 | Distal muscle weakness | Very frequent (99-80%)"

Orphanet records distal muscle weakness as a very frequent HPO phenotype, matching the distal-predominant weakness described here.

Nervous System 3

Cognitive Impairment FREQUENT Cognitive impairment (HP:0100543)

Show evidence (2 references)

PMID:38454488 SUPPORT Human Clinical

"Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."

Directly documents cognitive impairment as a clinical manifestation in a genetically confirmed DM1 cohort.

ORPHA:273 SUPPORT Other

"HP:0100543 | Cognitive impairment | Frequent (79-30%)"

Orphanet records cognitive impairment as a frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

Excessive Daytime Somnolence VERY_FREQUENT Excessive daytime somnolence (HP:0001262)

Show evidence (2 references)

PMID:38454488 SUPPORT Human Clinical

"Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes."

Directly supports excessive daytime somnolence as a very frequent DM1 phenotype.

ORPHA:273 SUPPORT Other

"HP:0001262 | Excessive daytime somnolence | Very frequent (99-80%)"

Orphanet records excessive daytime somnolence as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

Insomnia OCCASIONAL Insomnia (HP:0100785)

Show evidence (1 reference)

PMID:38454488 SUPPORT Human Clinical

"Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."

Documents intermittent insomnia at 28.1% prevalence in a genetically confirmed DM1 cohort.

Respiratory 1

Respiratory Insufficiency OCCASIONAL Respiratory insufficiency (HP:0002093)

Show evidence (2 references)

PMID:30765255 SUPPORT Human Clinical

"respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing;"

Supports respiratory insufficiency as a common respiratory manifestation with restrictive and hypoventilation physiology.

ORPHA:273 SUPPORT Other

"HP:0002093 | Respiratory insufficiency | Occasional (29-5%)"

Orphanet records respiratory insufficiency as an occasional HPO phenotype for Steinert myotonic dystrophy / DM1.

Constitutional 1

Fatigue FREQUENT Fatigue (HP:0012378)

Show evidence (2 references)

PMID:38454488 SUPPORT Human Clinical

"Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features."

Directly documents fatigue as the third most prevalent DM1 clinical feature in a 64-patient genetically confirmed cohort.

ORPHA:273 SUPPORT Other

"HP:0012378 | Fatigue | Frequent (79-30%)"

Orphanet records fatigue as a frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

Other 2

Myotonia VERY_FREQUENT Myotonia with warm-up phenomenon (HP:0003740)

Show evidence (2 references)

PMID:18974556 SUPPORT Human Clinical

"Myotonia reflects a state of muscle fiber hyperexcitability. Impaired transmembrane conductance of either chloride or sodium ions results in myotonia."

Confirms myotonia as the defining feature resulting from ion channel dysfunction.

ORPHA:273 SUPPORT Other

"HP:0003740 | Myotonia with warm-up phenomenon | Very frequent (99-80%)"

Orphanet records myotonia with warm-up phenomenon as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

Cataracts VERY_FREQUENT Posterior subcapsular cataract (HP:0007787)

Show evidence (2 references)

PMID:6655188 SUPPORT Human Clinical

"Perhaps the most noteworthy of these is the distinctive myotonic cataract which often appears early on in the course of the disorder."

Supports cataract as an early and characteristic ocular manifestation of myotonic dystrophy.

ORPHA:273 SUPPORT Other

"HP:0007787 | Posterior subcapsular cataract | Very frequent (99-80%)"

Orphanet records posterior subcapsular cataract as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.

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Genetic Associations

1

DMPK (CTG Trinucleotide Repeat Expansion)

Show evidence (1 reference)

PMID:31326502 SUPPORT Human Clinical

"Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene."

Confirms the CTG expansion in DMPK as the causative mutation with genetic anticipation.

💊

Treatments

5

Anesthetic and Drug Precautions

Action: Anesthesia and drug precautions Ontology label: Pharmacotherapy NCIT:C15986

Several agents are contraindicated or hazardous in DM1 and should be avoided or used with caution, particularly perioperatively, given the risk of muscle, cardiac, and respiratory complications.

Show evidence (1 reference)

PMID:20301344 SUPPORT Human Clinical

"Cholesterol-lowering medications (i.e., statins), which can cause muscle pain and weakness; the anesthetic agent vecuronium; succinylcholine, propofol, and doxorubicin"

GeneReviews lists these agents among those to avoid in DM1; statins can cause muscle pain/weakness and the anesthetic agents carry perioperative risk.

Pharmacotherapy for Myotonia

Action: Pharmacotherapy NCIT:C15986

Mexiletine is the most commonly used antimyotonia agent. Other options include phenytoin and carbamazepine for symptomatic relief of myotonia.

Mechanism Target:

MODULATES CLCN1 Mis-splicing and Reduced Chloride Conductance — Mexiletine is symptomatic antimyotonia pharmacotherapy that reduces delayed relaxation downstream of the CLCN1/chloride-conductance myotonia branch.

Show evidence (1 reference)

PMID:20439846 SUPPORT Human Clinical

"Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia treatment in DM1."

Randomized crossover trials support mexiletine as symptomatic treatment for DM1 myotonia.

Cardiac Monitoring and Pacemaker

Action: surgical procedure MAXO:0000004

Regular cardiac monitoring with ECG and Holter is essential. Pacemaker or implantable cardioverter-defibrillator may be required for conduction defects or arrhythmias.

Supportive Care

Action: supportive care MAXO:0000950

Multidisciplinary care including physical therapy, speech therapy, respiratory support (non-invasive ventilation), and ophthalmologic surveillance.

Genetic Counseling

Action: genetic counseling MAXO:0000079

Genetic counseling is essential given autosomal dominant inheritance with anticipation. Congenital DM1 is almost exclusively maternally transmitted.

{ }

Source YAML

click to show

name: Myotonic Dystrophy Type 1
creation_date: "2026-03-06T00:00:00Z"
updated_date: "2026-04-28T06:32:51Z"
description: >
  Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is an autosomal
  dominant multisystem disorder caused by expansion of a CTG trinucleotide repeat
  in the 3'-untranslated region of the DMPK gene. It is the most common form of
  adult-onset muscular dystrophy. The expanded CUG repeat RNA is retained in nuclear
  foci where it sequesters MBNL1 splicing regulators, causing widespread
  mis-splicing of downstream target genes. Clinical features include myotonia,
  progressive muscle weakness and wasting, cardiac conduction defects, cataracts,
  endocrine abnormalities, and cognitive impairment. Disease severity generally
  correlates with repeat expansion size.
category: Mendelian
disease_term:
  preferred_term: Myotonic Dystrophy Type 1
  term:
    id: MONDO:0008056
    label: myotonic dystrophy type 1
parents:
- Muscular Dystrophy
- Trinucleotide Repeat Disorder
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0008056
      label: myotonic dystrophy type 1
    mapping_predicate: skos:exactMatch
    mapping_source: ORPHA:273
    mapping_justification: Orphanet lists MONDO:0008056 as an exact cross-reference for Steinert myotonic dystrophy / myotonic dystrophy type 1.
    consistency:
    - reference: ORPHA:273
      consistent: CONSISTENT
      notes: "MONDO:0008056 | Exact"
definitions:
- name: Orphanet disease definition
  definition_type: CASE_DEFINITION
  description: >
    Orphanet defines Steinert myotonic dystrophy / DM1 as a rare genetic
    multisystem disorder with muscle manifestations, early-onset cataracts, and
    cerebral, endocrine, cardiac, gastrointestinal, uterine, skin, and immunologic
    involvement across a broad onset spectrum.
  evidence:
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "A rare genetic multi-system disorder characterized by a wide range of muscle-related manifestations (muscle weakness, myotonia, early onset cataracts (before age 50) and systemic manifestations (cerebral, endocrine, cardiac, gastrointestinal tract, uterus, skin and immunologic involvement) that vary depending on the age of onset."
    explanation: Orphanet's definition supports the multisystem clinical framing of DM1 in this entry.
external_assertions:
- name: Orphanet Steinert myotonic dystrophy record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:273
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=273
  description: >
    Orphanet structured record for Steinert myotonic dystrophy / myotonic
    dystrophy type 1, including synonyms, definition, inheritance, natural
    history, epidemiology, HPO phenotypes, and cross-references.
  evidence:
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0008056 | Exact"
    explanation: Orphanet cross-references ORPHA:273 exactly to MONDO:0008056.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "OMIM:160900 | Exact"
    explanation: Orphanet cross-references ORPHA:273 exactly to OMIM:160900.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ICD-10:G71.1 | Narrower"
    explanation: Orphanet lists ICD-10 G71.1 as a narrower cross-reference for ORPHA:273.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ICD-11:8C71.0 | Narrower"
    explanation: Orphanet lists ICD-11 8C71.0 as a narrower cross-reference for ORPHA:273.
inheritance:
- name: Autosomal dominant inheritance
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: DM1 follows autosomal dominant inheritance.
  evidence:
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal dominant"
    explanation: Orphanet records autosomal dominant inheritance for Steinert myotonic dystrophy / DM1.
prevalence:
- population: Global
  percentage: "0.00927"
  evidence:
  - reference: PMID:35483324
    reference_title: "Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The pooled estimate of the prevalence of DM1 was 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000."
    explanation: Meta-analysis provides the pooled global DM1 prevalence estimate used for the percentage value.
  notes: Pooled global prevalence estimate of 9.27 per 100,000 individuals, with substantial geographic heterogeneity.
- population: Worldwide (Orphanet point prevalence)
  percentage: "0.01-0.05"
  notes: Orphanet reports a worldwide point-prevalence class of 1-5 per 10,000.
  evidence:
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-5 / 10 000 | Worldwide | Point prevalence | PMID:702021520,PMID:21364698"
    explanation: The Orphanet epidemiology table provides a worldwide point-prevalence class for Steinert myotonic dystrophy / DM1.
diagnosis:
- name: Clinical and Molecular Diagnosis
  description: >-
    Myotonic dystrophy type 1 is suspected from the characteristic pattern of
    myotonia, progressive distal muscle weakness, cataracts, and multisystem
    involvement, and is confirmed by molecular genetic testing for the DMPK
    CTG trinucleotide repeat expansion.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
  evidence:
  - reference: PMID:20301344
    reference_title: "Myotonic Dystrophy Type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of DM1 is suspected in individuals with characteristic muscle weakness and is confirmed by molecular genetic testing of DMPK. CTG repeat length exceeding 34 repeats is abnormal."
    explanation: >-
      GeneReviews defines the clinical-plus-molecular diagnostic criteria for DM1, confirmed by DMPK CTG repeat sizing.
progression:
- phase: Onset
  age_range: Antenatal through adulthood
  notes: Classic adult-onset form typically presents in second to fourth decade, while congenital DM1 can present before or at birth; Orphanet records onset categories from antenatal through adult.
  evidence:
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Antenatal"
    explanation: Orphanet records antenatal onset for Steinert myotonic dystrophy / DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Neonatal"
    explanation: Orphanet records neonatal onset for Steinert myotonic dystrophy / DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Infancy"
    explanation: Orphanet records infancy onset for Steinert myotonic dystrophy / DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Childhood"
    explanation: Orphanet records childhood onset for Steinert myotonic dystrophy / DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Adolescent"
    explanation: Orphanet records adolescent onset for Steinert myotonic dystrophy / DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Adult"
    explanation: Orphanet records adult onset for Steinert myotonic dystrophy / DM1.
pathophysiology:
- name: DMPK CTG Repeat Expansion
  description: >
    DM1 begins with an unstable CTG trinucleotide repeat expansion in the
    3'-untranslated region of DMPK. The repeat-expansion allele is germline,
    autosomal dominant, and becomes more unstable across generations and across
    tissues, providing the initiating mutation for downstream RNA toxicity.
  genes:
  - preferred_term: DMPK
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  evidence:
  - reference: PMID:31326502
    reference_title: "Molecular genetics of congenital myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene."
    explanation: Establishes the causal repeat expansion and anticipation.
  - reference: PMID:15065017
    reference_title: "Myotonic dystrophy: RNA pathogenesis comes into focus."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "In 1992, the mutation responsible for DM1 was identified as a CTG expansion located in the 3' untranslated region of the dystrophia myotonica-protein kinase gene (DMPK)."
    explanation: Review-level evidence confirms the initiating DMPK 3'-UTR CTG expansion.
  downstream:
  - target: Toxic CUG RNA Nuclear Foci
    causal_link_type: DIRECT
    description: The expanded DMPK allele is transcribed into CUG repeat-containing RNA that accumulates in nuclear foci.
  - target: SIX5/DMPK Locus Effects in Lens
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Repeat expansion near SIX5 may alter local chromatin and SIX5 transcription.
    description: The repeat expansion sits adjacent to SIX5, supporting a parallel locus-dosage branch for cataract susceptibility.
- name: Toxic CUG RNA Nuclear Foci
  description: >
    The expanded DMPK repeat is transcribed into CUG repeat-containing RNA that
    forms nuclear foci. These foci are the central toxic RNA species in DM1,
    retaining mutant RNA in the nucleus and recruiting RNA-binding proteins that
    normally regulate adult splicing programs.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  - preferred_term: cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: nucleus
    term:
      id: GO:0005634
      label: nucleus
  evidence:
  - reference: PMID:12351998
    reference_title: "Myotonic syndromes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both types of myotonic dystrophy the expanded repeat is transcribed and the RNA produced from the mutant allele is retained in nuclear inclusions. Recent studies suggest that the mutant RNA has a toxic effect on muscle fibers by interfering with the essential functions of the myonucleus, such as RNA processing."
    explanation: Confirms the toxic RNA gain-of-function mechanism in myotonic dystrophy.
  - reference: PMID:15065017
    reference_title: "Myotonic dystrophy: RNA pathogenesis comes into focus."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "the clinical features common to both diseases are caused by a gain-of-function RNA mechanism in which the CUG and CCUG repeats alter cellular function, including alternative splicing of various genes."
    explanation: Supports the toxic RNA gain-of-function mechanism and its connection to altered splicing.
  downstream:
  - target: Splicing Factor Imbalance and Fetal Spliceopathy
    causal_link_type: DIRECT
    description: Expanded CUG RNA foci sequester MBNL proteins and shift CELF1/MBNL balance, producing widespread developmental splice reversion.
- name: Splicing Factor Imbalance and Fetal Spliceopathy
  description: >
    Expanded CUG RNA sequesters MBNL family proteins in nuclear foci and is
    accompanied by increased CELF1/CUGBP1 activity in affected tissues. The
    resulting loss of adult MBNL activity and CELF1/MBNL imbalance causes
    fetal-pattern alternative splicing across skeletal muscle, heart, endocrine,
    and CNS transcripts.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  - preferred_term: cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: nucleus
    term:
      id: GO:0005634
      label: nucleus
  evidence:
  - reference: PMID:18974556
    reference_title: "Myotonic disorders."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mutant RNA sequesters MBNL1, a splice regulator protein and depletes MBNL1 from the nucleoplasm. Loss of MBNL1 results in altered splicing of ClC-1 mRNA."
    explanation: Describes the MBNL1 depletion mechanism that drives DM1 spliceopathy.
  - reference: PMID:27063795
    reference_title: "Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The pathogenesis of DM involves a RNA gain-of-function mechanism caused by expression of mutant RNAs containing hundred to thousands of CUG or CCUG repeats that interfere with the splicing of other pre-mRNAs through dysfunction of two classes of RNA-binding proteins."
    explanation: Supports the broader spliceopathy mechanism downstream of expanded repeat RNA.
  downstream:
  - target: CLCN1 Mis-splicing and Reduced Chloride Conductance
    causal_link_type: DIRECT
    description: MBNL1 depletion causes CLCN1 mis-splicing, loss of functional ClC-1 chloride channel, and skeletal muscle hyperexcitability.
  - target: CACNA1S Mis-splicing and Excitation-Contraction Coupling Defect
    causal_link_type: DIRECT
    description: Mis-splicing of CaV1.1/CACNA1S alters excitation-contraction coupling in skeletal muscle and contributes to weakness.
  - target: Dysphagia
    causal_link_type: DIRECT
    description: Oropharyngeal skeletal muscle spliceopathy contributes to swallowing dysfunction in DM1.
  - target: INSR Splicing Shift and Insulin Resistance
    causal_link_type: DIRECT
    description: Aberrant insulin receptor splicing favors the lower-signaling IR-A isoform in skeletal muscle.
  - target: SCN5A Splicing Shift and Cardiac Excitability Loss
    causal_link_type: DIRECT
    description: Cardiac spliceopathy shifts SCN5A toward a fetal exon 6A isoform with reduced excitability.
  - target: CNS Spliceopathy and Tau Dysregulation
    causal_link_type: DIRECT
    description: MBNL1/2 sequestration in the CNS alters brain splicing programs, including MAPT/tau-related transcripts.
- name: CLCN1 Mis-splicing and Reduced Chloride Conductance
  description: >
    MBNL1 sequestration causes mis-splicing of the chloride channel gene CLCN1,
    leading to loss of functional ClC-1 chloride channels in skeletal muscle
    membranes. Reduced chloride conductance causes membrane hyperexcitability
    and myotonia.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  evidence:
  - reference: PMID:18974556
    reference_title: "Myotonic disorders."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Altered splice products do not encode functional ClC-1 protein. Subsequent loss of chloride conductance in muscle membrane causes myotonia in the myotonic dystrophies."
    explanation: Directly links CLCN1 mis-splicing to reduced chloride conductance and myotonia.
  downstream:
  - target: Myotonia
    causal_link_type: DIRECT
    description: Loss of functional ClC-1 chloride conductance causes the muscle hyperexcitability phenotype.
- name: CACNA1S Mis-splicing and Excitation-Contraction Coupling Defect
  description: >
    DM1 spliceopathy represses inclusion of CACNA1S/CaV1.1 exon 29 in skeletal
    muscle. CaV1.1 controls excitation-contraction coupling, so this splice
    shift changes calcium-channel gating and contributes to progressive muscle
    weakness and myopathic changes.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  evidence:
  - reference: PMID:22140091
    reference_title: "Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The extent of E29 skipping correlated with severity of weakness in tibialis anterior muscle of DM1 patients."
    explanation: Human muscle data link CACNA1S exon 29 skipping to weakness severity.
  downstream:
  - target: Progressive Muscle Weakness
    causal_link_type: DIRECT
    description: Altered CaV1.1 gating impairs excitation-contraction coupling and contributes to progressive skeletal muscle weakness.
  - target: Fatigue
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Skeletal muscle spliceopathy contributes to impaired muscle performance and reduced activity tolerance.
    description: Excitation-contraction coupling defects and myopathic changes can contribute to fatigue in DM1.
  - target: Respiratory Muscle and Central Drive Dysfunction
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Weakness of respiratory muscles contributes to restrictive ventilatory impairment.
    description: The same skeletal muscle weakness branch can involve respiratory muscles and worsen ventilatory capacity.
- name: INSR Splicing Shift and Insulin Resistance
  description: >
    Aberrant splicing of insulin receptor pre-mRNA in DM1 skeletal muscle favors
    the lower-signaling IR-A isoform, reducing metabolic insulin responsiveness
    and contributing to insulin resistance and diabetes mellitus.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  evidence:
  - reference: PMID:11528389
    reference_title: "Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "alternative splicing of the insulin receptor (IR) pre-mRNA is aberrantly regulated in DM1 skeletal muscle tissue, resulting in predominant expression of the lower-signaling nonmuscle isoform (IR-A)."
    explanation: Directly supports the INSR splice shift that produces an insulin-resistant skeletal muscle phenotype.
  downstream:
  - target: Insulin Resistance and Diabetes
    causal_link_type: DIRECT
    description: Predominant IR-A expression lowers insulin signaling in skeletal muscle and contributes to glucose intolerance and diabetes.
- name: SCN5A Splicing Shift and Cardiac Excitability Loss
  description: >
    In DM1 heart tissue, MBNL-dependent spliceopathy shifts SCN5A from the adult
    exon 6B isoform toward the fetal exon 6A isoform. The resulting Nav1.5
    channel has reduced excitability, providing a mutation-to-cardiac conduction
    defect branch in the pathograph.
  cell_types:
  - preferred_term: cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  evidence:
  - reference: PMID:27063795
    reference_title: "Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A."
    explanation: Human heart RNA-seq identifies the SCN5A splice shift.
  downstream:
  - target: Cardiac Conduction Defects
    causal_link_type: DIRECT
    description: Reduced excitability of the fetal SCN5A/Nav1.5 isoform contributes to conduction delay and arrhythmia.
- name: CNS Spliceopathy and Tau Dysregulation
  description: >
    DM1 affects the central nervous system through MBNL1/2 sequestration and
    aberrant brain splicing. MAPT/tau transcript dysregulation and abnormal tau
    deposition provide a mechanistic bridge to cognitive and behavioral impairment.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: RNA splicing
    term:
      id: GO:0008380
      label: RNA splicing
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:32407311
    reference_title: "Differences in splicing defects between the grey and white matter in myotonic dystrophy type 1 patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This leads to the sequestration of splicing factors such as muscleblind-like 1/2 (MBNL1/2) and aberrant splicing in the central nervous system."
    explanation: Human brain study supports CNS MBNL sequestration and aberrant splicing.
  - reference: PMID:36331500
    reference_title: "Neuropathology of classic myotonic dystrophy type 1 is characterized by both early initiation of primary age-related tauopathy of the hippocampus and unique 3-repeat tauopathy of the brainstem."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau protein in the CNS."
    explanation: Human neuropathology links MAPT spliceopathy and CNS tau deposition.
  downstream:
  - target: Cognitive Impairment
    causal_link_type: DIRECT
    description: CNS spliceopathy and tau dysregulation provide a mechanistic basis for cognitive impairment in DM1.
  - target: Excessive Daytime Somnolence
    causal_link_type: DIRECT
    description: CNS MBNL sequestration and aberrant brain splicing contribute to hypersomnia in DM1.
  - target: Insomnia
    causal_link_type: DIRECT
    description: CNS MBNL sequestration and disrupted sleep-wake circuitry contribute to sleep fragmentation and insomnia in DM1.
- name: SIX5/DMPK Locus Effects in Lens
  description: >
    The DM1 CTG repeat lies near SIX5, and repeat-associated local chromatin or
    transcriptional effects can reduce SIX5 dosage. Mouse Six5 loss produces
    progressive ocular cataracts, supporting a parallel lens branch in addition
    to toxic RNA spliceopathy.
  evidence:
  - reference: PMID:10802668
    reference_title: "Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Our results demonstrate that the rate and severity of cataract formation is inversely related to Six5 dosage and is temporally progressive."
    explanation: Six5 dosage model supports a cataract mechanism connected to the DMPK/SIX5 locus.
  downstream:
  - target: Cataracts
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Reduced SIX5 dosage alters lens ion homeostasis and promotes progressive cataract formation.
    description: DMPK/SIX5 locus effects provide a mutation-to-lens opacity path.
- name: Respiratory Muscle and Central Drive Dysfunction
  description: >
    Respiratory morbidity in DM1 reflects both peripheral respiratory muscle
    weakness and central respiratory drive involvement. The result is commonly
    restrictive ventilatory dysfunction with alveolar hypoventilation, chronic
    hypercapnia, and sleep-disordered breathing.
  cell_types:
  - preferred_term: skeletal muscle cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  evidence:
  - reference: PMID:30765255
    reference_title: "Respiratory dysfunction in myotonic dystrophy type 1: A systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing;"
    explanation: Systematic review supports respiratory dysfunction and its major physiologic components in DM1.
  downstream:
  - target: Respiratory Insufficiency
    causal_link_type: DIRECT
    description: Restrictive ventilatory impairment and hypoventilation manifest clinically as respiratory insufficiency.
phenotypes:
- category: Musculoskeletal
  name: Myotonia
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >
    Myotonia, the hallmark symptom, is characterized by delayed relaxation of
    skeletal muscle after contraction. Patients describe stiffness that improves
    with repeated muscle contractions (warm-up phenomenon).
  phenotype_term:
    preferred_term: Myotonia with warm-up phenomenon
    term:
      id: HP:0003740
      label: Myotonia with warm-up phenomenon
  evidence:
  - reference: PMID:18974556
    reference_title: "Myotonic disorders."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Myotonia reflects a state of muscle fiber hyperexcitability. Impaired transmembrane conductance of either chloride or sodium ions results in myotonia."
    explanation: Confirms myotonia as the defining feature resulting from ion channel dysfunction.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003740 | Myotonia with warm-up phenomenon | Very frequent (99-80%)"
    explanation: Orphanet records myotonia with warm-up phenomenon as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Musculoskeletal
  name: Progressive Muscle Weakness
  frequency: VERY_FREQUENT
  description: >
    Progressive skeletal muscle weakness and wasting, particularly affecting
    distal muscles initially (grip, ankle dorsiflexors), with later involvement
    of proximal muscles and facial muscles.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:28780071
    reference_title: "Myotonic dystrophy: candidate small molecule therapeutics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene."
    explanation: DM1 is a neuromuscular disorder with progressive weakness as a core feature.
  - reference: PMID:22140091
    reference_title: "Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The extent of E29 skipping correlated with severity of weakness in tibialis anterior muscle of DM1 patients."
    explanation: Provides a direct molecular correlation between CaV1.1 mis-splicing and weakness severity.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002460 | Distal muscle weakness | Very frequent (99-80%)"
    explanation: Orphanet records distal muscle weakness as a very frequent HPO phenotype, matching the distal-predominant weakness described here.
- category: Musculoskeletal
  name: Fatigue
  frequency: FREQUENT
  description: >
    Fatigue is among the most common complaints in DM1, affecting the majority of
    patients and substantially impairing quality of life and daily activity.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: PMID:38454488
    reference_title: "Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features."
    explanation: Directly documents fatigue as the third most prevalent DM1 clinical feature in a 64-patient genetically confirmed cohort.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
    explanation: Orphanet records fatigue as a frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Ophthalmologic
  name: Cataracts
  frequency: VERY_FREQUENT
  description: >
    Posterior subcapsular cataracts are a characteristic finding, often present
    before age 50. Iridescent multicolored opacities (Christmas tree cataracts)
    are pathognomonic for DM1.
  phenotype_term:
    preferred_term: Posterior subcapsular cataract
    term:
      id: HP:0007787
      label: Posterior subcapsular cataract
  evidence:
  - reference: PMID:6655188
    reference_title: "Cataracts in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Perhaps the most noteworthy of these is the distinctive myotonic cataract which often appears early on in the course of the disorder."
    explanation: Supports cataract as an early and characteristic ocular manifestation of myotonic dystrophy.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007787 | Posterior subcapsular cataract | Very frequent (99-80%)"
    explanation: Orphanet records posterior subcapsular cataract as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Cardiac
  name: Cardiac Conduction Defects
  frequency: VERY_FREQUENT
  description: >
    Cardiac involvement includes conduction abnormalities (first-degree AV block,
    bundle branch block), arrhythmias, and cardiomyopathy. Cardiac complications
    are a leading cause of death in DM1.
  phenotype_term:
    preferred_term: Cardiac conduction abnormality
    term:
      id: HP:0031546
      label: Cardiac conduction abnormality
  evidence:
  - reference: PMID:27063795
    reference_title: "Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM."
    explanation: Supports conduction delay and arrhythmia as major cardiac manifestations of myotonic dystrophy.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0031546 | Cardiac conduction abnormality | Very frequent (99-80%)"
    explanation: Orphanet records cardiac conduction abnormality as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Endocrine
  name: Insulin Resistance and Diabetes
  frequency: OCCASIONAL
  description: >
    Endocrine manifestations include insulin resistance, diabetes mellitus,
    hypogonadism in males, and thyroid dysfunction.
  phenotype_term:
    preferred_term: Diabetes mellitus
    term:
      id: HP:0000819
      label: Diabetes mellitus
  evidence:
  - reference: PMID:11528389
    reference_title: "Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "People with DM1 have an unusual form of insulin resistance caused by a defect in skeletal muscle."
    explanation: Supports the insulin resistance branch that contributes to the diabetes phenotype in DM1.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000819 | Diabetes mellitus | Occasional (29-5%)"
    explanation: Orphanet records diabetes mellitus as an occasional HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Neurologic
  name: Cognitive Impairment
  frequency: FREQUENT
  description: >
    Central nervous system involvement includes cognitive impairment, apathy,
    and other behavioral manifestations in adult DM1.
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:38454488
    reference_title: "Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."
    explanation: Directly documents cognitive impairment as a clinical manifestation in a genetically confirmed DM1 cohort.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100543 | Cognitive impairment | Frequent (79-30%)"
    explanation: Orphanet records cognitive impairment as a frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Neurologic
  name: Excessive Daytime Somnolence
  frequency: VERY_FREQUENT
  description: >
    Excessive daytime sleepiness is common in DM1 and can substantially affect
    daily functioning.
  phenotype_term:
    preferred_term: Excessive daytime somnolence
    term:
      id: HP:0001262
      label: Excessive daytime somnolence
  evidence:
  - reference: PMID:38454488
    reference_title: "Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes."
    explanation: Directly supports excessive daytime somnolence as a very frequent DM1 phenotype.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001262 | Excessive daytime somnolence | Very frequent (99-80%)"
    explanation: Orphanet records excessive daytime somnolence as a very frequent HPO phenotype for Steinert myotonic dystrophy / DM1.
- category: Neurologic
  name: Insomnia
  frequency: OCCASIONAL
  description: >
    Intermittent insomnia has been documented in DM1, contributing to overall
    sleep disturbance alongside excessive daytime somnolence.
  phenotype_term:
    preferred_term: Insomnia
    term:
      id: HP:0100785
      label: Insomnia
  evidence:
  - reference: PMID:38454488
    reference_title: "Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."
    explanation: Documents intermittent insomnia at 28.1% prevalence in a genetically confirmed DM1 cohort.
- category: Neurologic
  name: Dysphagia
  frequency: FREQUENT
  description: >
    Swallowing difficulty is a frequent multisystem manifestation of DM1 and can
    require nutritional support in advanced cases.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:38454488
    reference_title: "Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment."
    explanation: Directly supports dysphagia as a frequent clinical manifestation in DM1.
- category: Respiratory
  name: Respiratory Insufficiency
  frequency: OCCASIONAL
  description: >
    Respiratory failure from weakness of the diaphragm and intercostal muscles
    is a major cause of morbidity and mortality.
  phenotype_term:
    preferred_term: Respiratory insufficiency
    term:
      id: HP:0002093
      label: Respiratory insufficiency
  evidence:
  - reference: PMID:30765255
    reference_title: "Respiratory dysfunction in myotonic dystrophy type 1: A systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing;"
    explanation: Supports respiratory insufficiency as a common respiratory manifestation with restrictive and hypoventilation physiology.
  - reference: ORPHA:273
    reference_title: "Steinert myotonic dystrophy (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002093 | Respiratory insufficiency | Occasional (29-5%)"
    explanation: Orphanet records respiratory insufficiency as an occasional HPO phenotype for Steinert myotonic dystrophy / DM1.
genetic:
- name: DMPK
  association: CTG Trinucleotide Repeat Expansion
  presence: Positive
  notes: >
    Expansion of CTG repeats in the 3'-UTR of DMPK on chromosome 19q13.3.
    Normal alleles have 5-34 repeats; affected individuals have 50 to >1000 repeats.
    Congenital DM1 is associated with very large expansions (>1000 repeats).
    Genetic anticipation occurs, with repeat length increasing across generations.
  evidence:
  - reference: PMID:31326502
    reference_title: "Molecular genetics of congenital myotonic dystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene."
    explanation: Confirms the CTG expansion in DMPK as the causative mutation with genetic anticipation.
treatments:
- name: Anesthetic and Drug Precautions
  description: >-
    Several agents are contraindicated or hazardous in DM1 and should be
    avoided or used with caution, particularly perioperatively, given the
    risk of muscle, cardiac, and respiratory complications.
  treatment_term:
    preferred_term: Anesthesia and drug precautions
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:20301344
    reference_title: "Myotonic Dystrophy Type 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cholesterol-lowering medications (i.e., statins), which can cause muscle pain and weakness; the anesthetic agent vecuronium; succinylcholine, propofol, and doxorubicin"
    explanation: >-
      GeneReviews lists these agents among those to avoid in DM1; statins can
      cause muscle pain/weakness and the anesthetic agents carry
      perioperative risk.
- name: Pharmacotherapy for Myotonia
  description: >
    Mexiletine is the most commonly used antimyotonia agent. Other options include
    phenytoin and carbamazepine for symptomatic relief of myotonia.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_mechanisms:
  - target: CLCN1 Mis-splicing and Reduced Chloride Conductance
    treatment_effect: MODULATES
    description: >
      Mexiletine is symptomatic antimyotonia pharmacotherapy that reduces delayed
      relaxation downstream of the CLCN1/chloride-conductance myotonia branch.
    evidence:
    - reference: PMID:20439846
      reference_title: "Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia treatment in DM1."
      explanation: Randomized crossover trials support mexiletine as symptomatic treatment for DM1 myotonia.
- name: Cardiac Monitoring and Pacemaker
  description: >
    Regular cardiac monitoring with ECG and Holter is essential. Pacemaker or
    implantable cardioverter-defibrillator may be required for conduction defects
    or arrhythmias.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Supportive Care
  description: >
    Multidisciplinary care including physical therapy, speech therapy, respiratory
    support (non-invasive ventilation), and ophthalmologic surveillance.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
- name: Genetic Counseling
  description: >
    Genetic counseling is essential given autosomal dominant inheritance with
    anticipation. Congenital DM1 is almost exclusively maternally transmitted.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
datasets:
references:
- reference: PMID:20301344
  title: "Myotonic Dystrophy Type 1."
  tags:
  - GeneReviews
  findings: []

📚

References & Deep Research

References

1

PMID:20301344

Myotonic Dystrophy Type 1.

No top-level findings curated for this source.

Deep Research

1

Falcon ▸

Myotonic Dystrophy Type 1 (DM1) — Disease Characteristics Research Report

Edison Scientific Literature 36 citations 2026-04-25T22:26:41.275526

Myotonic Dystrophy Type 1 (DM1) — Disease Characteristics Research Report

Target disease: Myotonic dystrophy type 1 (DM1)
Category: Mendelian (repeat-expansion disorder)
MONDO: MONDO_0008056 (via Open Targets disease mapping) (berengercurrias2023pluripotentstemcells pages 1-2)

1. Disease Information

1.1 Concise overview

Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic neuromuscular disorder characterized by myotonia and progressive muscle weakness, with frequent involvement of the heart (conduction disease/arrhythmias), eyes (cataracts), endocrine/metabolic systems (e.g., insulin resistance/diabetes), gastrointestinal function, and the central nervous system. DM1 is caused by an unstable CTG repeat expansion in the 3′ untranslated region (3′UTR) of the DMPK gene, and disease pathogenesis is largely driven by toxic expanded-repeat RNA that perturbs RNA-binding proteins and alternative splicing (“spliceopathy”). (hale2023dynamicsandvariability pages 1-2, almeida2023promisingaav.u7snrnasvectors pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)

Direct abstract quote (mechanism + overview): A 2023 Frontiers paper states: “DM1 is caused by a CTG repeat expansion in the 3′UTR region of the DMPK gene that sequesters muscleblind-like proteins, blocking their splicing activity and forming nuclear RNA foci. Consequently, many genes have their splicing reversed to a fetal pattern.” (Almeida et al., 2023-06, https://doi.org/10.3389/fcell.2023.1181040) (almeida2023promisingaav.u7snrnasvectors pages 1-2)

1.2 Key identifiers (and common names)

Disease name	Synonyms	MONDO ID	OMIM	Orphanet	MeSH	ICD-10/ICD-11	Notes
Myotonic Dystrophy Type 1 (DM1)	Steinert disease; Steinert’s myotonic dystrophy; myotonic dystrophy type I; MDI	MONDO_0008056	160900	273	D009223	Not available from the provided evidence	OMIM #160900 explicitly reported in peer-reviewed DM1 sources; Steinert/MDI naming used in epidemiology and review papers; MeSH D009223 reported in a DM1 registry record; Open Targets reports MONDO_0008056 and Orphanet_273 for DM1. URLs: https://doi.org/10.3389/fneur.2024.1493570 ; https://doi.org/10.1186/s13023-024-03114-z ; https://doi.org/10.1186/s13023-024-03114-z ; https://doi.org/10.3390/healthcare12080838 (abati2024cardiacriskand pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, hernaez2024prevalenceofsteinert’s pages 1-2, NCT06979024 chunk 1)

Table: This table summarizes the core identifiers and common alternative names for Myotonic Dystrophy Type 1. It is useful for harmonizing disease records across ontology, registry, and literature sources while noting that ICD codes were not established from the provided evidence.

Additional identifier evidence from recent literature: - OMIM: DM1 = #160900 (reported explicitly in multiple 2023–2024 sources) (abati2024cardiacriskand pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2) - Orphanet concept: “Steinert myotonic dystrophy” (Open Targets reports Orphanet_273 mapping) (berengercurrias2023pluripotentstemcells pages 1-2)

ICD-10/ICD-11: Not established from the provided evidence; would require an ICD browser or coding guidance not retrieved in this tool run.

1.3 Synonyms and alternative names

Commonly used synonyms in recent sources include: - Steinert disease / Steinert’s myotonic dystrophy (hernaez2024prevalenceofsteinert’s pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2) - Myotonic dystrophy type I / MDI (hernaez2024prevalenceofsteinert’s pages 1-2)

1.4 Evidence sources: individual vs aggregated

DM1 knowledge in this report is derived from: - Aggregated disease-level resources/registries: Madrid rare disease registry (SIERMA) used for population estimates (2010–2017) (hernaez2024prevalenceofsteinert’s pages 1-2); China DM1 patient registry (ClinicalTrials.gov observational cohort) (NCT06979024 chunk 1) - Cohort-based clinical genetics studies: multicenter Chinese cohort (n=211) (zhong2024clinicalfeaturesand pages 1-2) - Mechanistic disease modeling studies: patient-derived myoblasts, iPSC/hPSC models, and mouse models (almeida2023promisingaav.u7snrnasvectors pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 8-9)

2. Etiology

2.1 Disease causal factors

Primary cause: Germline CTG trinucleotide repeat expansion in the DMPK gene 3′UTR (autosomal dominant). (hale2023dynamicsandvariability pages 1-2, almeida2023promisingaav.u7snrnasvectors pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)

Repeat-size categories (clinical correlation; indicative, not absolute): - Healthy alleles: ~5–37 CTGs (almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2) - Premutation: ~38–49 CTGs (almeida2023promisingaav.u7snrnasvectors pages 1-2) - Symptomatic: typically >50 CTGs, with larger expansions associated with earlier onset and more severe phenotypes, including congenital forms that can exceed 1,000 CTGs. (almeida2023promisingaav.u7snrnasvectors pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)

2.2 Risk factors

Genetic risk factors - Repeat length and instability: CTG repeat length correlates with phenotype severity and age of onset, complicated by somatic instability (repeat length varies by tissue/age). (stoodley2023applicationofantisense pages 1-2, ionova2024thestudyof pages 1-2) - Anticipation: Intergenerational repeat expansion contributes to earlier onset and increased severity in successive generations, with congenital disease often associated with large maternal expansions. (hale2023dynamicsandvariability pages 1-2, ionova2024thestudyof pages 1-2)

Non-genetic modifiers and clinical risk factors - Cardiopulmonary complications are major determinants of morbidity/mortality; surveillance and early interventions are emphasized in care recommendations and clinical management sources. (ricci2024assessmentofthe pages 17-20, abati2024cardiacriskand pages 1-2)

2.3 Protective factors / modifier factors

Protective “factors” in DM1 primarily refer to genetic modifiers that mitigate repeat instability or molecular toxicity.

Interrupted/variant repeat tracts and epigenetic context: A Mexican reference cohort reported interrupted CTG repeat tracts in 2.8% of carriers and associated these interruptions with milder phenotypes and reduced instability (cohort details in excerpt). (cerecedozapata2025fifteenyearsof pages 15-16)
Epigenetic variability (methylation) at the DM1 locus: DMPK expanded alleles are flanked by CpG islands; variant repeats may influence methylation patterns and phenotypic variability (summarized in recent molecular work). (ionova2024thestudyof pages 1-2)

2.4 Gene–environment interactions

No robust, specific gene–environment interaction mechanisms were directly established from the retrieved evidence. However, dietary context can exacerbate metabolic pathology in model systems (see Mechanisms/Pathophysiology). (stoodley2023applicationofantisense pages 1-2)

3. Phenotypes

3.1 Core phenotype spectrum (multisystem)

Adult/classical DM1 commonly includes: - Myotonia and progressive distal muscle weakness (hale2023dynamicsandvariability pages 1-2, stoodley2023applicationofantisense pages 1-2) - Cardiac conduction defects/arrhythmias (hale2023dynamicsandvariability pages 1-2, abati2024cardiacriskand pages 1-2) - Early cataracts (hale2023dynamicsandvariability pages 1-2) - CNS impairment (cognitive/behavioral) (hale2023dynamicsandvariability pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2)

Congenital DM1 (CDM) can present at birth with: - Neonatal hypotonia, respiratory failure, feeding difficulty, and congenital features (e.g., clubfoot), with motor improvement in early childhood reported in natural history. (hale2023dynamicsandvariability pages 1-2)

3.2 Quantitative phenotype frequencies and statistics (prioritize 2024)

Large multicenter Chinese Han DM1 cohort (genetically confirmed n=211; detailed phenotyping n=64; enrollment 2020–2023) reported: (Zhong et al., 2024-03, Orphanet J Rare Dis, https://doi.org/10.1186/s13023-024-03114-z) - In the detailed cohort, muscle weakness 92.2%, myotonia 85.9%, fatigue 73.4% (zhong2024clinicalfeaturesand pages 1-2) - Daytime sleepiness 70.3%; dysphagia 43.8%; cognitive impairment 25%; intermittent insomnia 28.1%; dyspnea 23.4%; diabetes 17.2%; tumors 4.7% (zhong2024clinicalfeaturesand pages 1-2) - Supportive interventions/markers: cataract surgery 14.1%, wheelchair use 7.8%, ventilatory support 4.7%, gastric tube 1.6% (zhong2024clinicalfeaturesand pages 1-2) - Mean ESS 10.50 (SD 6.18) and mean FSS 42.02 (SD 15.01) (zhong2024clinicalfeaturesand pages 5-7)

A cropped table of the Zhong et al. cohort summarizing frequencies across CTG strata was retrieved (Table 1) (zhong2024clinicalfeaturesand media 408fef39).

Pediatric (congenital/childhood onset) sleep/behavior cohort (Italy; n=46) reported: - Daytime sleepiness/disrupted sleep in 30% of children (CDM and ChDM), with associations to autism traits, executive function, and disease burden measures. (Trucco et al., 2024-09, https://doi.org/10.3390/jcm13185459) (hernaez2024prevalenceofsteinert’s pages 1-2)

3.3 Quality-of-life and functional impact

DM1 is associated with reduced physical activity and aerobic capacity, contributing to adverse body composition.

A prospective case-control study (n=15 DM1 vs 15 matched controls) found: - Total energy expenditure 23% lower in DM1; steps/day 63% lower (median 3090 vs 8283 steps/24 h); and reduced VO2peak (22 vs 33 mL/min/kg). (Joosten et al., 2023-05, J Neuromuscul Dis, https://doi.org/10.3233/JND-230036) (hernaez2024prevalenceofsteinert’s pages 1-2)

3.4 Suggested HPO terms (examples; non-exhaustive)

Myotonia → HP:0002486
Distal muscle weakness → HP:0002460 (distal muscle weakness)
Progressive muscle wasting → HP:0003202
Cardiac conduction defect → HP:0001678
Cardiac arrhythmia → HP:0011675
Cataract → HP:0000518
Dysphagia → HP:0002015
Excessive daytime sleepiness → HP:0002329
Respiratory insufficiency/failure (congenital) → HP:0002093/HP:0002878
Cognitive impairment → HP:0100543

(These HPO IDs are standard ontology mappings; specific HPO IDs were not enumerated in the retrieved papers and should be validated against the HPO browser when integrating into a KB.)

4. Genetic/Molecular Information

4.1 Causal gene

DMPK (DM1 protein kinase); pathogenic mechanism triggered by expanded repeat in 3′UTR. (almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2)

Open Targets disease-target associations identify DMPK as the top associated target and report DM1 locus antisense RNA (DM1-AS) as another association in the locus context (mapping evidence). (berengercurrias2023pluripotentstemcells pages 1-2)

4.2 Pathogenic variant class

Repeat expansion: CTG expansion in the DMPK 3′UTR (structural/repeat-expansion class; germline). (hale2023dynamicsandvariability pages 1-2, stoodley2023applicationofantisense pages 1-2)

Somatic mosaicism/instability: A major complexity in DM1 is that repeat lengths expand over time and differ by tissue (somatic instability), complicating genotype–phenotype correlations. (ionova2024thestudyof pages 1-2)

4.3 Modifier genes and molecular modifiers

MBNL family sequestration is primary; additional regulators include CELF1 upregulation/hyperphosphorylation as part of spliceopathy amplification. (berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)
Core spliceosomal proteins as modifiers: A 2024 Human Molecular Genetics study identified core spliceosomal proteins (e.g., SNRPD2) as modifiers capable of reducing DMPK expression and partially rescuing mis-splicing in cellular models (modifier class concept). (stoodley2023applicationofantisense pages 1-2)

4.4 Epigenetics

Epigenetic variability at CpG islands flanking the expansion has been implicated as a contributor to phenotypic variability, particularly in the context of variant repeat interruptions and parental origin effects. (ionova2024thestudyof pages 1-2)

5. Environmental Information

No infectious etiologies apply.

Environmental/lifestyle factors are not causal, but lifestyle may influence secondary metabolic phenotypes. For example, a liver-specific DM1 mouse model showed that high-fat/high-sugar diets exacerbate lipid accumulation and susceptibility to MAFLD-like phenotypes in the context of CUGexp RNA toxicity. (Dewald et al., 2024-10, Nat Commun, https://doi.org/10.1038/s41467-024-53378-z) (stoodley2023applicationofantisense pages 1-2)

6. Mechanism / Pathophysiology

6.1 Current mechanistic model (key concepts and definitions)

RNA toxicity / RNA gain-of-function model: The expanded DMPK allele is transcribed, producing expanded CUG repeat RNA that forms nuclear foci and sequesters MBNL proteins, leading to depletion of functional MBNL in the nucleoplasm and widespread defects in alternative splicing. (hale2023dynamicsandvariability pages 1-2, almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2)

CELF1 dysregulation: Stress signaling pathways can increase CELF1 activity, and an MBNL/CELF1 imbalance drives persistent fetal splicing patterns across hundreds of transcripts. (berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)

Direct abstract quote (pathogenic chain): “DM1 is caused by a CTG repeat expansion in the 3′UTR region of the DMPK gene that sequesters muscleblind-like proteins… forming nuclear RNA foci… [and] splicing [is] reversed to a fetal pattern.” (Almeida et al., 2023-06, https://doi.org/10.3389/fcell.2023.1181040) (almeida2023promisingaav.u7snrnasvectors pages 1-2)

6.2 Downstream pathways and tissue-specific consequences

Spliceopathy targets with clinical relevance: Mis-spliced transcripts include CLCN1 (myotonia), SCN5A (cardiac conduction), BIN1, and INSR (metabolic phenotype), among others. (hale2023dynamicsandvariability pages 1-2, stoodley2023applicationofantisense pages 1-2)

Developmental dynamics (congenital DM1): RNA-seq of congenital DM1 skeletal muscle across pediatric development showed an MBNL-dependent mis-splicing signature with a triphasic pattern: severe mis-splicing in infancy, improvement in early childhood, and variability in adolescence. (Hale et al., 2023-10, https://doi.org/10.1093/hmg/ddac254) (hale2023dynamicsandvariability pages 1-2)

6.3 Suggested GO biological processes (examples)

Alternative mRNA splicing via spliceosome → GO:0000380
mRNA processing → GO:0006397
Regulation of RNA splicing → GO:0043484
Muscle contraction (downstream functional impairment) → GO:0006936

6.4 Suggested CL cell types (examples)

Skeletal muscle myoblast / myotube → CL:0000056 (myoblast; verify exact CL term usage)
Cardiomyocyte → CL:0000746
Motor neuron (CNS involvement) → CL:0000100

(As with HPO, CL/GO IDs should be validated in ontology browsers; the mechanistic linkage is supported by DM1 literature cited above.)

7. Anatomical Structures Affected

Primary/commonly affected systems: - Skeletal muscle (UBERON:0001134) (almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2) - Heart (UBERON:0000948) including conduction system (abati2024cardiacriskand pages 1-2) - Brain/CNS (UBERON:0000955) (hale2023dynamicsandvariability pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2) - Eye lens (UBERON:0000962) — cataracts (hale2023dynamicsandvariability pages 1-2) - Respiratory system (UBERON:0001004) — respiratory insufficiency/failure (hale2023dynamicsandvariability pages 1-2, ricci2024assessmentofthe pages 17-20)

Subcellular localization (core lesion): nuclear RNA foci (nucleus; GO CC:0005634) and RNA-binding protein sequestration. (almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2)

8. Temporal Development

8.1 Onset

DM1 spans congenital, childhood/juvenile, and adult-onset forms; congenital DM1 can present at birth and is often linked to large intergenerational expansions. (hale2023dynamicsandvariability pages 1-2, ionova2024thestudyof pages 1-2)

In congenital DM1, hallmark adult features can be absent early, and early-life symptoms include neonatal hypotonia and respiratory failure. (hale2023dynamicsandvariability pages 1-2)

8.2 Progression

DM1 is typically progressive across neuromuscular and systemic domains. The congenital DM1 transcriptome/spliceopathy can show dynamic changes across pediatric development, suggesting time windows for intervention/biomarkers. (hale2023dynamicsandvariability pages 1-2)

9. Inheritance and Population

9.1 Inheritance

Autosomal dominant inheritance with anticipation (intergenerational repeat expansion and earlier onset). (hale2023dynamicsandvariability pages 1-2, ionova2024thestudyof pages 1-2)
Maternal transmission enrichment and maternal expansions are often linked to congenital forms. (hale2023dynamicsandvariability pages 1-2, ionova2024thestudyof pages 1-2)

9.2 Epidemiology (recent data)

Recent studies show considerable geographic variation: - Global/Europe estimates: ~1 in 8,000 cited in mechanistic and clinical sources (almeida2023promisingaav.u7snrnasvectors pages 1-2, abati2024cardiacriskand pages 1-2) - Community of Madrid (Spain) population registry: 14.4 per 100,000 (2010–2017; n=1101; mean age 47.8; 49.1% women). (Hernáez et al., 2024-04, https://doi.org/10.3390/healthcare12080838) (hernaez2024prevalenceofsteinert’s pages 1-2) - North Ossetia-Alania families study: prevalence 14.17 per 100,000 (Ossetians) and 18.74 per 100,000 (Ingush); anticipation and correlation of CTG length with onset/severity; higher maternal transmission frequency. (Ionova et al., 2024-09, https://doi.org/10.3390/ijms25179734) (ionova2024thestudyof pages 1-2) - Chinese multicenter cohort: minimal prevalence estimate 0.13/100,000 in the authors’ ascertainment context; cohort suggests possible underdiagnosis or population differences. (zhong2024clinicalfeaturesand pages 2-5)

10. Diagnostics

10.1 Clinical and electrophysiologic testing

EMG can show myotonic discharges; in a Chinese cohort, EMG abnormalities were reported in 92.2% (195/211). (zhong2024clinicalfeaturesand pages 2-5)

10.2 Genetic testing (repeat expansion testing)

Core diagnostic test: detection of CTG repeat expansion at the DMPK locus.

Zhong et al. used TP-PCR and flanking PCR to size peak CTG repeats (range 92–1945) and diagnose DM1. (zhong2024clinicalfeaturesand pages 2-5)
Registry study notes genotyping can use triplet-primed PCR or long-read sequencing, with DM1 confirmation as CTG repeats >50. (NCT06979024 chunk 1)

Emerging diagnostics (long-read): Repeat expansion disorders increasingly use long-read sequencing for repeat length, composition, mosaicism, and methylation assessment; the DM1 testing landscape is moving in that direction (general diagnostic perspective; not DM1-only). (berengercurrias2023pluripotentstemcells pages 1-2)

10.3 Imaging and biomarkers

Cardiac imaging biomarker candidate: In a small retrospective cohort, DM1 patients had higher cardiac extracellular volume (ECV) on CMR (a fibrosis-associated metric), suggesting CMR ECV as a marker of subclinical cardiac involvement. (Abati et al., 2024-11, https://doi.org/10.3389/fneur.2024.1493570) (abati2024cardiacriskand pages 1-2)

10.4 Differential diagnosis

Not enumerated in the retrieved evidence; clinically, DM2 (CNBP CCTG expansion) is a principal genetic differential (noted in review/imaging context). (abati2024cardiacriskand pages 1-2)

11. Outcome / Prognosis

Major causes of morbidity/mortality: cardiopulmonary complications. - Cardiac dysrhythmias and conduction disease are prominent; one recent review-style paper notes dysrhythmias can be implicated in a large fraction of patients and are a leading cause of mortality, second to respiratory failure. (abati2024cardiacriskand pages 1-2, ricci2024assessmentofthe pages 17-20)

A recent synthesis cites median survival around 59–60 years, with respiratory failure and adverse cardiac events as leading causes of death. (misquitta2024investigatingthetherapeutic pages 9-13)

12. Treatment

12.1 Current real-world management (symptomatic/supportive)

DM1 management is multidisciplinary and largely symptomatic.

Cardiac surveillance/intervention: surveillance is emphasized; device therapy (pacemaker/ICD) may be indicated for conduction disease and tachyarrhythmias. (ricci2024assessmentofthe pages 17-20)

Respiratory support: non-invasive ventilation (BiPAP/CPAP), respiratory physiotherapy, and supportive interventions can improve quality of life and survival in respiratory involvement. (ricci2024assessmentofthe pages 17-20)

Myotonia pharmacotherapy: mexiletine is a commonly used antimyotonia therapy; symptomatic agents require ECG assessment due to cardiac risk considerations. A care/outcome measures source reports “Class 1 evidence” supporting mexiletine 150–200 mg three times daily for myotonia. (ricci2024assessmentofthe pages 17-20)

Sleepiness: modafinil or methylphenidate may be used for disabling daytime sleepiness (symptomatic). (ricci2024assessmentofthe pages 17-20)

MAXO term suggestions (examples): - Antiarrhythmic drug therapy (mexiletine) → MAXO:0000105 (drug therapy; confirm specific MAXO term) - Cardiac pacemaker implantation → MAXO:0000621 (device implantation; verify) - Noninvasive ventilation → MAXO:0000504 (ventilatory support; verify) - Physical therapy/rehabilitation → MAXO:0000019 (rehabilitation; verify)

(Exact MAXO IDs should be verified; MAXO mappings were not provided in the retrieved documents.)

12.2 Recent developments and latest research (2023–2024 priority)

12.2.1 RNA-/gene-targeting approaches (preclinical/translation)

AAV-delivered antisense (U7snRNA) targeting DMPK/CTG tracts: Patient-derived myoblasts treated with AAV8.U7snRNA antisense constructs showed reduced RNA foci, MBNL relocalization, and broad splicing correction (RNA-seq), supporting long-lasting delivery strategies beyond systemic ASOs. (Almeida et al., 2023-06, https://doi.org/10.3389/fcell.2023.1181040) (almeida2023promisingaav.u7snrnasvectors pages 1-2)

Antisense conjugates review (delivery focus): Research is focusing on improving ASO biodistribution using lipid/cell-penetrating peptide/antibody conjugation to improve muscle (including cardiac) delivery; CNS delivery remains challenging. (Stoodley et al., 2023-01, https://doi.org/10.3390/ijms24032697) (stoodley2023applicationofantisense pages 1-2, stoodley2023applicationofantisense pages 8-9)

AntimiR strategy (MBNL1 derepression): A 2024 Science Advances study in primary DM1 myoblasts reports that antimiRs targeting miR-23b and miR-218 can boost MBNL1 and improve RNA toxicity readouts and myoblast phenotypes; the abstract notes a leading antimiR reversed 68% of dysregulated genes and also reduced DMPK transcripts and ribonuclear foci. (Cerro-Herreros et al., 2024-10, https://doi.org/10.1126/sciadv.adn6525) (stoodley2023applicationofantisense pages 1-2)

12.2.2 Clinical trials (registry evidence; 2023–2024 status emphasis)

Avidity Biosciences (AOC 1001 / del-desiran) programs - AOC 1001 study in adult DM1: NCT05027269, Phase 1/2, COMPLETED, enrollment 39. (ClinicalTrials.gov) (NCT02858908 chunk 1) - Open-label extension: NCT05479981, Phase 2, COMPLETED, enrollment 37. (ClinicalTrials.gov) (NCT02858908 chunk 1) - Global Phase 3 study del-desiran: NCT06411288, Phase 3, ACTIVE_NOT_RECRUITING, enrollment 159. (ClinicalTrials.gov) (NCT02858908 chunk 1) - Global Phase 3 open-label extension: NCT07008469, Phase 3, ENROLLING_BY_INVITATION, enrollment 230. (ClinicalTrials.gov) (NCT02858908 chunk 1)

Gene therapy trial - Sanofi AAV gene therapy: SAR446268, NCT06844214, Phase 1/2, RECRUITING, enrollment 32. (ClinicalTrials.gov) (NCT02858908 chunk 1)

Small-molecule/repurposed therapy trials (examples) - Tideglusib trial: NCT02858908, Phase 2, COMPLETED, enrollment 16; endpoints include safety and multiple functional measures; results posted in 2025 per registry metadata. (ClinicalTrials.gov) (NCT02858908 chunk 1) - Mexiletine (once-daily PR) trial: NCT06523400, Phase 3, RECRUITING, enrollment 176. (ClinicalTrials.gov) (NCT02858908 chunk 1)

Important limitation: Quantitative efficacy results for AOC 1001/del-desiran, VX-670, SAR446268, and mexiletine PR were not available in the retrieved evidence snippets (trial registry metadata were retrieved; full results would require additional extraction). (NCT02858908 chunk 1)

13. Prevention

13.1 Primary prevention

No primary prevention exists for a germline Mendelian repeat-expansion disorder other than reproductive options.

13.2 Secondary prevention (early detection)

Cascade testing in families and early molecular confirmation are core strategies due to anticipation and variable onset. (ionova2024thestudyof pages 1-2)

13.3 Tertiary prevention (complication prevention)

Routine cardiac surveillance and proactive management of conduction disease to reduce sudden death risk. (ricci2024assessmentofthe pages 17-20, abati2024cardiacriskand pages 1-2)
Proactive respiratory monitoring and ventilation support where indicated. (ricci2024assessmentofthe pages 17-20)

13.4 Genetic counseling and reproductive options

A Mexican national reference cohort described implementation of clinical and molecular evaluation including predictive testing, prenatal diagnosis, and preimplantation genetic diagnosis, but with limited uptake due to legal, cultural, and cost barriers. (cerecedozapata2025fifteenyearsof pages 15-16)

14. Other Species / Natural Disease

No naturally occurring DM1 in non-human species was established from the retrieved evidence (e.g., OMIA/veterinary sources were not retrieved in this run). This section is therefore not available from current evidence.

15. Model Organisms

15.1 Cellular and stem cell models

Human pluripotent stem cell (hPSC/iPSC) models are used for disease mechanism decoding and drug discovery, motivated by DM1 multisystem involvement beyond skeletal muscle. (Bérenger-Currias et al., 2023-02, https://doi.org/10.3390/cells12040571) (berengercurrias2023pluripotentstemcells pages 1-2)

15.2 Mouse models

DMSXL and related models carrying human DMPK with large CTG expansions (>1,000) have been used to study CNS delivery strategies (mentioned in antisense conjugate review context). (stoodley2023applicationofantisense pages 8-9)
Tissue-targeted models (e.g., liver-specific expression of CUGexp RNA) reproduce metabolic and drug-metabolism phenotypes and link CUGexp RNA toxicity to hepatic dysfunction. (Dewald et al., 2024-10, https://doi.org/10.1038/s41467-024-53378-z) (stoodley2023applicationofantisense pages 1-2)

Expert synthesis / analysis (authoritative interpretation)

Mechanism-guided therapeutic logic: The convergence of evidence across cohorts and models supports DM1 as an RNA-mediated spliceopathy. This coherently explains multisystem involvement, since DMPK is broadly expressed and MBNL/CELF-driven splicing programs are fundamental in multiple tissues. (almeida2023promisingaav.u7snrnasvectors pages 1-2, berengercurrias2023pluripotentstemcells pages 1-2, stoodley2023applicationofantisense pages 1-2)
Why delivery dominates translational risk: ASOs can correct foci/splicing in models but face systemic delivery limitations in human muscle; the 2023–2024 literature emphasizes conjugation, viral delivery, and alternative nucleic-acid modalities to overcome biodistribution barriers. (almeida2023promisingaav.u7snrnasvectors pages 1-2, stoodley2023applicationofantisense pages 1-2, stoodley2023applicationofantisense pages 8-9)
Clinical heterogeneity is biologically grounded: Anticipation, tissue mosaicism, and repeat interruptions/methylation provide plausible explanations for substantial inter-individual variability and complicate prognosis based on blood repeat length alone. (ionova2024thestudyof pages 1-2)

Key gaps (not resolved in retrieved evidence)

ICD-10/ICD-11 codes and a definitive MeSH term specific to “DM1” (beyond MeSH Myotonic Dystrophy D009223) were not retrieved. (NCT06979024 chunk 1)
Outcome results for several major contemporary trials (AOC 1001/del-desiran Phase 3; VX-670; SAR446268) were not available in the evidence snippets. (NCT02858908 chunk 1)
Cross-species natural disease evidence (OMIA) and comprehensive differential diagnosis lists were not retrieved.

References

(berengercurrias2023pluripotentstemcells pages 1-2): Noémie Bérenger-Currias, Cécile Martinat, and Sandrine Baghdoyan. Pluripotent stem cells in disease modeling and drug discovery for myotonic dystrophy type 1. Cells, 12:571, Feb 2023. URL: https://doi.org/10.3390/cells12040571, doi:10.3390/cells12040571. This article has 10 citations.
(hale2023dynamicsandvariability pages 1-2): Melissa A Hale, Kameron Bates, Marina Provenzano, and Nicholas E Johnson. Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development. Human Molecular Genetics, 32:1413-1428, Oct 2023. URL: https://doi.org/10.1093/hmg/ddac254, doi:10.1093/hmg/ddac254. This article has 23 citations and is from a domain leading peer-reviewed journal.
(almeida2023promisingaav.u7snrnasvectors pages 1-2): C. Almeida, F. Robriquet, T. Vetter, N. Huang, Reid Neinast, Lumariz Hernández-Rosario, D. Rajakumar, W. Arnold, K. McBride, K. Flanigan, Robert B. Weiss, N. Wein, M. Bartoli, N. Motohashi, O. Hernández-Hernández, Mexico Guillermo Ibarra Ibarra, CF Almeida, T. Vetter, WD Arnold, K. McBride, KM Flanigan, Robriquet Vetter Huang © 2023 Almeida, Arnold Rajakumar, and Flanigan Weiss Wein. This McBride. Promising aav.u7snrnas vectors targeting dmpk improve dm1 hallmarks in patient-derived cell lines. Frontiers in Cell and Developmental Biology, Jun 2023. URL: https://doi.org/10.3389/fcell.2023.1181040, doi:10.3389/fcell.2023.1181040. This article has 8 citations.
(stoodley2023applicationofantisense pages 1-2): Jessica Stoodley, Francisco Vallejo-Bedia, David Seone-Miraz, Manuel Debasa-Mouce, Matthew J. A. Wood, and Miguel A. Varela. Application of antisense conjugates for the treatment of myotonic dystrophy type 1. International Journal of Molecular Sciences, 24:2697, Jan 2023. URL: https://doi.org/10.3390/ijms24032697, doi:10.3390/ijms24032697. This article has 28 citations.
(abati2024cardiacriskand pages 1-2): Elena Abati, Claudia Alberti, Valentina Tambè, Anastasia Esseridou, Giacomo Pietro Comi, Stefania Corti, Giovanni Meola, and Francesco Secchi. Cardiac risk and myocardial fibrosis assessment with cardiac magnetic resonance in patients with myotonic dystrophy. Frontiers in Neurology, Nov 2024. URL: https://doi.org/10.3389/fneur.2024.1493570, doi:10.3389/fneur.2024.1493570. This article has 4 citations and is from a peer-reviewed journal.
(hernaez2024prevalenceofsteinert’s pages 1-2): Leticia Hernáez, A. C. Zoni, M. Domínguez-Berjón, M. Esteban-Vasallo, C. Domínguez-González, P. Serrano, and On Behalf Of The Dm-Cm Working Group. Prevalence of steinert’s myotonic dystrophy and utilization of healthcare services: a population-based cross-sectional study. Healthcare, 12:838, Apr 2024. URL: https://doi.org/10.3390/healthcare12080838, doi:10.3390/healthcare12080838. This article has 2 citations.
(NCT06979024 chunk 1): A Registered Observational Cohort Study of Myotonic Dystrophy Type 1. First Affiliated Hospital of Fujian Medical University. 2008. ClinicalTrials.gov Identifier: NCT06979024
(zhong2024clinicalfeaturesand pages 1-2): Huahua Zhong, Li Zeng, Xuefan Yu, Qing Ke, Jihong Dong, Yan Chen, Lijun Luo, Xueli Chang, Junhong Guo, Yiqi Wang, Hui Xiong, Rongrong Liu, Changxia Liu, Jibao Wu, Jie Lin, Jianying Xi, Wenhua Zhu, Song Tan, Fuchen Liu, Jiahong Lu, Chongbo Zhao, and Sushan Luo. Clinical features and genetic spectrum of a multicenter chinese cohort with myotonic dystrophy type 1. Orphanet Journal of Rare Diseases, Mar 2024. URL: https://doi.org/10.1186/s13023-024-03114-z, doi:10.1186/s13023-024-03114-z. This article has 2 citations and is from a peer-reviewed journal.
(stoodley2023applicationofantisense pages 8-9): Jessica Stoodley, Francisco Vallejo-Bedia, David Seone-Miraz, Manuel Debasa-Mouce, Matthew J. A. Wood, and Miguel A. Varela. Application of antisense conjugates for the treatment of myotonic dystrophy type 1. International Journal of Molecular Sciences, 24:2697, Jan 2023. URL: https://doi.org/10.3390/ijms24032697, doi:10.3390/ijms24032697. This article has 28 citations.
(ionova2024thestudyof pages 1-2): Sofya A. Ionova, Aysylu F. Murtazina, Andrey A. Marakhonov, Olga A. Shchagina, Nina V. Ryadninskaya, Inna S. Tebieva, Vitaly V. Kadyshev, Artem O. Borovikov, Evgeny K. Ginter, Sergey I. Kutsev, and Rena A. Zinchenko. The study of the inheritance mechanisms of myotonic dystrophy type 1 (dm1) in families from the republic of north ossetia-alania. International Journal of Molecular Sciences, 25:9734, Sep 2024. URL: https://doi.org/10.3390/ijms25179734, doi:10.3390/ijms25179734. This article has 3 citations.
(ricci2024assessmentofthe pages 17-20): FS Ricci. Assessment of the central nervous system involvement in neuromuscular disorders: the evolution of outcome measures in childhood rare diseases. Unknown journal, 2024.
(cerecedozapata2025fifteenyearsof pages 15-16): César M. Cerecedo-Zapata, Araceli Guerra-Grajeda, Luz C. Márquez-Quiróz, Paola Arciga-Portela, Rosa E. Escobar-Cedillo, Guadalupe E. Jiménez-Gutiérrez, Óscar A. Pérez-Méndez, Jorge S. Velasco-Flores, Blanca A. Barredo-Prieto, Norberto Leyva-García, Bulmaro Cisneros, Nadia M. Murillo-Melo, and Jonathan J. Magaña. Fifteen years of myotonic dystrophy type 1 in mexico: clinical, molecular, and socioeconomic insights from a national reference cohort. Genes, 16:1515, Dec 2025. URL: https://doi.org/10.3390/genes16121515, doi:10.3390/genes16121515. This article has 0 citations.
(zhong2024clinicalfeaturesand pages 5-7): Huahua Zhong, Li Zeng, Xuefan Yu, Qing Ke, Jihong Dong, Yan Chen, Lijun Luo, Xueli Chang, Junhong Guo, Yiqi Wang, Hui Xiong, Rongrong Liu, Changxia Liu, Jibao Wu, Jie Lin, Jianying Xi, Wenhua Zhu, Song Tan, Fuchen Liu, Jiahong Lu, Chongbo Zhao, and Sushan Luo. Clinical features and genetic spectrum of a multicenter chinese cohort with myotonic dystrophy type 1. Orphanet Journal of Rare Diseases, Mar 2024. URL: https://doi.org/10.1186/s13023-024-03114-z, doi:10.1186/s13023-024-03114-z. This article has 2 citations and is from a peer-reviewed journal.
(zhong2024clinicalfeaturesand media 408fef39): Huahua Zhong, Li Zeng, Xuefan Yu, Qing Ke, Jihong Dong, Yan Chen, Lijun Luo, Xueli Chang, Junhong Guo, Yiqi Wang, Hui Xiong, Rongrong Liu, Changxia Liu, Jibao Wu, Jie Lin, Jianying Xi, Wenhua Zhu, Song Tan, Fuchen Liu, Jiahong Lu, Chongbo Zhao, and Sushan Luo. Clinical features and genetic spectrum of a multicenter chinese cohort with myotonic dystrophy type 1. Orphanet Journal of Rare Diseases, Mar 2024. URL: https://doi.org/10.1186/s13023-024-03114-z, doi:10.1186/s13023-024-03114-z. This article has 2 citations and is from a peer-reviewed journal.
(zhong2024clinicalfeaturesand pages 2-5): Huahua Zhong, Li Zeng, Xuefan Yu, Qing Ke, Jihong Dong, Yan Chen, Lijun Luo, Xueli Chang, Junhong Guo, Yiqi Wang, Hui Xiong, Rongrong Liu, Changxia Liu, Jibao Wu, Jie Lin, Jianying Xi, Wenhua Zhu, Song Tan, Fuchen Liu, Jiahong Lu, Chongbo Zhao, and Sushan Luo. Clinical features and genetic spectrum of a multicenter chinese cohort with myotonic dystrophy type 1. Orphanet Journal of Rare Diseases, Mar 2024. URL: https://doi.org/10.1186/s13023-024-03114-z, doi:10.1186/s13023-024-03114-z. This article has 2 citations and is from a peer-reviewed journal.
(misquitta2024investigatingthetherapeutic pages 9-13): Naomi Misquitta. Investigating the therapeutic potential of amp-activated protein kinase in myotonic dystrophy type 1. Dissertation, Nov 2024. URL: https://doi.org/10.20381/ruor-30683, doi:10.20381/ruor-30683. This article has 0 citations.
(NCT02858908 chunk 1): Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy. AMO Pharma Limited. 2016. ClinicalTrials.gov Identifier: NCT02858908

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Myotonic Dystrophy Type 1 (DM1) — Disease Characteristics Research Report

1. Disease Information

1.1 Concise overview

1.2 Key identifiers (and common names)

1.3 Synonyms and alternative names

1.4 Evidence sources: individual vs aggregated

2. Etiology

2.1 Disease causal factors

2.2 Risk factors

2.3 Protective factors / modifier factors

2.4 Gene–environment interactions

3. Phenotypes

3.1 Core phenotype spectrum (multisystem)

3.2 Quantitative phenotype frequencies and statistics (prioritize 2024)

3.3 Quality-of-life and functional impact

3.4 Suggested HPO terms (examples; non-exhaustive)

4. Genetic/Molecular Information

4.1 Causal gene

4.2 Pathogenic variant class

4.3 Modifier genes and molecular modifiers

4.4 Epigenetics

5. Environmental Information

6. Mechanism / Pathophysiology

6.1 Current mechanistic model (key concepts and definitions)

6.2 Downstream pathways and tissue-specific consequences

6.3 Suggested GO biological processes (examples)

6.4 Suggested CL cell types (examples)

7. Anatomical Structures Affected

8. Temporal Development

8.1 Onset

8.2 Progression

9. Inheritance and Population

9.1 Inheritance

9.2 Epidemiology (recent data)

10. Diagnostics

10.1 Clinical and electrophysiologic testing

10.2 Genetic testing (repeat expansion testing)

10.3 Imaging and biomarkers

10.4 Differential diagnosis

11. Outcome / Prognosis

12. Treatment

12.1 Current real-world management (symptomatic/supportive)

12.2 Recent developments and latest research (2023–2024 priority)

12.2.1 RNA-/gene-targeting approaches (preclinical/translation)

12.2.2 Clinical trials (registry evidence; 2023–2024 status emphasis)

13. Prevention

13.1 Primary prevention

13.2 Secondary prevention (early detection)

13.3 Tertiary prevention (complication prevention)

13.4 Genetic counseling and reproductive options

14. Other Species / Natural Disease

15. Model Organisms

15.1 Cellular and stem cell models

15.2 Mouse models

Expert synthesis / analysis (authoritative interpretation)

Key gaps (not resolved in retrieved evidence)