Dystrophinopathies (DMD & BMD)
Dystrophinopathies are X-linked recessive muscle disorders caused by pathogenic variants in the DMD gene on chromosome Xp21.2, encoding the protein dystrophin. The DMD gene is the largest known human gene, spanning approximately 2.4 megabases with 79 exons. Dystrophinopathies encompass a clinical spectrum ranging from severe Duchenne muscular dystrophy (DMD), through intermediate phenotypes, to milder Becker muscular dystrophy (BMD), as well as isolated dilated cardiomyopathy and manifesting female carriers. DMD is the most common childhood muscular dystrophy, with an incidence of approximately 1 in 3,500–5,000 live male births. Historically managed with supportive care and corticosteroids alone, the therapeutic landscape has expanded dramatically since 2016 with the approval of exon-skipping antisense oligonucleotides, a microdystrophin gene therapy, a dissociative steroid (vamorolone), and a histone deacetylase inhibitor (givinostat). Despite these advances, none of the available treatments are curative, and multidisciplinary care remains the cornerstone of management.
Bottom Line
- Genetics: Pathogenic variants in DMD (Xp21.2)—the largest human gene (79 exons); deletions account for ~65%, duplications ~10%, and point mutations ~25%; the reading-frame rule predicts severity in ~90% of cases
- DMD phenotype: Onset ages 2–5 years with proximal weakness, Gowers sign, calf pseudohypertrophy, and CK >1,000 U/L (often >10,000); loss of ambulation by ~12–13 years (delayed 2–3 years with corticosteroids); progressive cardiomyopathy and respiratory failure
- BMD phenotype: Milder course; ambulatory into adulthood (often beyond age 16); cardiomyopathy may be the predominant or presenting feature and can be disproportionate to skeletal muscle weakness
- Female carriers: ~8% develop dilated cardiomyopathy due to skewed X-inactivation; carrier testing and cardiac surveillance are mandatory when a male is diagnosed
- Corticosteroids: Standard of care for DMD; three options—prednisone/prednisolone, deflazacort, and vamorolone (FDA-approved 2023, ages ≥2 years); daily dosing is superior to intermittent regimens (FOR-DMD trial)
- Exon-skipping therapies: Eteplirsen (exon 51), golodirsen and viltolarsen (exon 53), casimersen (exon 45)—collectively applicable to ~30% of DMD patients; modest dystrophin restoration with variable functional benefit
- Gene therapy: Delandistrogene moxeparvovec (Elevidys)—AAVrh74-delivered microdystrophin; FDA-approved for ambulatory boys ≥4 years; boxed warning for fatal acute liver failure added in 2025; indication restricted to ambulatory patients
- Multidisciplinary care: Coordinated cardiac, pulmonary, orthopedic, endocrine, GI, and neuropsychiatric management is essential across all stages of disease
Dystrophin Gene and Reading-Frame Rule
The DMD gene spans 2.4 Mb on chromosome Xp21.2, comprising 79 exons that encode the 427 kDa dystrophin protein. Dystrophin functions as a critical structural link between the intracellular actin cytoskeleton and the extracellular matrix, via the dystrophin-associated protein complex (DAPC) at the sarcolemma. This complex includes the dystroglycans, sarcoglycans, syntrophins, and dystrobrevins. Loss or severe reduction of dystrophin destabilizes the sarcolemma during muscle contraction, leading to calcium influx, oxidative stress, chronic inflammation, and progressive replacement of muscle with fibrotic and fatty tissue.
The Reading-Frame Rule
The reading-frame rule, first described by Monaco and colleagues in 1988, is the primary molecular predictor of dystrophinopathy severity:
- Frameshift (out-of-frame) variants: Disrupt the mRNA reading frame, producing an unstable transcript subject to nonsense-mediated decay—resulting in absent or near-absent dystrophin (>95% reduction on Western blot). This pattern is characteristic of DMD.
- In-frame variants: Preserve the reading frame, producing a truncated but partially functional dystrophin protein. As long as the critical N-terminal actin-binding, cysteine-rich, and C-terminal domains are preserved, sarcolemmal integrity is partially maintained—resulting in the milder BMD phenotype.
- Exceptions (~10% of cases): Early frameshift variants may produce a BMD phenotype through alternative translation initiation sites or spontaneous exon skipping; conversely, in-frame deletions disrupting critical domains (N-terminal, cysteine-rich, or C-terminal) can behave clinically like DMD.
Pathogenic Variant Distribution
- Large deletions: ~65% of all dystrophinopathy variants; cluster in two hotspot regions (exons 45–55 and exons 2–20)
- Large duplications: ~10%; also cluster in the 5′ end of the gene
- Point variants (nonsense, missense, splice-site, small insertions/deletions): ~25%; require gene sequencing beyond deletion/duplication analysis
- De novo variants: Account for approximately one-third of cases—absence of family history does not exclude the diagnosis
- Deep intronic variants: Rare (<1%); may require RNA analysis from muscle biopsy for identification
Clinical Presentation: Duchenne Muscular Dystrophy
DMD is the severe end of the dystrophinopathy spectrum, with symptom onset typically between ages 2 and 5 years. Boys present with gross motor delays, including delayed walking (often achieved by 14–18 months), frequent falls, difficulty climbing stairs, toe walking, and a waddling gait.
Classic Examination Findings
- Gowers sign: The child uses the arms to "climb up" the legs when rising from the floor, reflecting proximal lower extremity and trunk weakness
- Calf pseudohypertrophy: Enlarged calves due to replacement of muscle with fibrotic and fatty tissue
- Neck flexion weakness: Often detectable early in the disease course
- Proximal > distal weakness: Symmetric, affecting hip girdle and shoulder girdle; feet cannot clear the ground during attempted running
- Preserved Achilles reflexes: Present until later in the disease, unlike spinal muscular atrophy where reflexes are diffusely diminished early
Natural History
| Stage | Age Range | Key Features |
|---|---|---|
| Early ambulatory | 2–6 years | Motor delays, Gowers sign, waddling gait, CK peaks (often >10,000 U/L); may present with speech delay or autism |
| Late ambulatory | 6–12 years | Progressive difficulty with stairs and rising from floor; increasing falls; initiation of corticosteroids and consideration of gene therapy |
| Early non-ambulatory | 12–18 years | Loss of ambulation (~12–13 years without steroids; ~14–16 years with steroids); scoliosis risk; progressive upper limb weakness |
| Late non-ambulatory | >18 years | Severe cardiomyopathy, respiratory failure requiring NIV, progressive dysphagia; CK declines as muscle mass is lost |
Less Common Presentations
Dystrophinopathy may first come to attention through unexpected pathways:
- Incidental transaminitis: Elevated AST and ALT from muscle breakdown (not hepatic injury); gamma-glutamyl transferase (GGT) will be normal, distinguishing muscle from liver as the source
- Speech delay or autism spectrum disorder: Dystrophin is expressed in the brain; neurodevelopmental disorders are more prevalent in boys with DMD than in the general population
- Newborn screening: Pilot programs in New York, Ohio, Minnesota, and Massachusetts screen for DMD using CK-MM in dried blood spots or DMD genetic testing; however, no FDA-approved therapy can be used before age 2 years
Becker Muscular Dystrophy
BMD represents the milder end of the spectrum, caused by in-frame DMD variants that produce a reduced quantity or truncated but partially functional dystrophin protein. Key distinguishing features include:
- Later onset: Symptoms typically appear after age 5 years, often in the second decade of life
- Prolonged ambulation: Patients remain ambulatory beyond age 16 years; some walk independently into their 40s–60s
- Cardiomyopathy may predominate: Dilated cardiomyopathy can be the presenting or primary feature, sometimes with minimal skeletal muscle weakness; cardiomyopathy severity may be disproportionate to limb weakness
- Intermediate phenotype: Loss of ambulation between ages 13 and 16 years; these patients may require muscle biopsy with immunohistochemistry and Western blot to characterize dystrophin expression and guide prognosis
- CK elevation: Typically elevated but lower than in DMD; significant overlap exists between DMD and BMD CK ranges—CK alone cannot reliably distinguish the two
Female Carriers and DMD-Associated Cardiomyopathy
Heterozygous female carriers of DMD pathogenic variants may develop clinically significant disease due to skewed X-chromosome inactivation, where the normal X chromosome is preferentially silenced in affected tissues.
- Dilated cardiomyopathy: Estimated prevalence ~8% in female carriers; may develop without skeletal muscle symptoms; cardiac MRI can detect subclinical myocardial fibrosis (late gadolinium enhancement)
- Symptomatic weakness: Manifesting carriers present with proximal weakness, exercise intolerance, or hyperCKemia; severity ranges from mild limb-girdle weakness to a DMD-like phenotype
- Mandatory evaluation: When a boy is diagnosed with dystrophinopathy, carrier testing must be offered to the mother; confirmed carriers require baseline and periodic cardiac surveillance (ECG, echocardiogram or cardiac MRI)
Key Screening Recommendations
- Any boy with motor delay, calf hypertrophy, and proximal weakness should have CK checked first—CK >1,000 U/L warrants genetic testing for DMD
- Any boy with autism or speech delay should have CK screening to exclude dystrophinopathy
- Elevated AST/ALT with normal GGT in a boy suggests muscle (not liver) as the source—check CK
- All female carriers require baseline cardiac evaluation and periodic surveillance
- One-third of cases are de novo—negative family history does not exclude the diagnosis
Diagnostic Evaluation
Genetic Testing
In the appropriate clinical context (CK >1,000 U/L with compatible examination findings), genetic testing is the next step. The testing strategy reflects the distribution of variant types:
| Testing Method | Detects | Coverage | Notes |
|---|---|---|---|
| MLPA / chromosomal microarray | Large deletions and duplications | ~75% of variants | Traditionally the first-tier test; identifies exon-level copy number changes |
| Next-generation sequencing (NGS) | Point variants, small insertions/deletions, splice-site variants | ~25% of variants | Required after negative MLPA; newer NGS panels detect both large and small variants in one step |
| Muscle biopsy | Dystrophin expression (immunohistochemistry, Western blot); RNA analysis | Deep intronic variants (<1%) | Reserved for genetically unresolved cases; helpful in intermediate phenotypes to characterize dystrophin quantity and quality |
Sponsored no-charge genetic testing programs are available, including DETECT-MD (Invitae), which accepts patients with elevated CK, progressive proximal weakness, calf hypertrophy, or dystrophic muscle biopsy findings. The Leiden DMD Mutation Database provides a reading-frame checker to predict phenotype from specific variants.
Differential Diagnosis
Key Differential Diagnoses
- Spinal muscular atrophy type 3: Proximal weakness after age 18 months; may have calf hypertrophy; CK typically in the hundreds (not thousands); diffusely hypoactive reflexes; low CMAP amplitudes and neurogenic EMG pattern; detected by newborn screening in all 50 US states
- Sarcoglycanopathies (LGMD-R3 through R5): Autosomal recessive; closely mimic dystrophinopathies with proximal weakness, calf hypertrophy, elevated CK, and cardiomyopathy
- Emery-Dreifuss muscular dystrophy: Early proximal contractures (elbows, knees, ankles), scapuloperoneal weakness pattern, and cardiac conduction defects
- Congenital muscular dystrophies: Hypotonia and weakness from birth; may have structural brain abnormalities (dystroglycanopathies)
- Congenital myasthenic syndromes and juvenile myasthenia gravis: Fatigable weakness; normal or mildly elevated CK; decremental response on RNS
Corticosteroid Therapy
Corticosteroids remain the standard of care for DMD, preserving ambulation for an additional 2–3 years and delaying the onset of respiratory failure, cardiomyopathy, scoliosis, and loss of upper limb function. Initiation is recommended between ages 3 and 5 years. Three formulations are currently available:
| Agent | Dosing | FDA Status | Key Considerations |
|---|---|---|---|
| Prednisone / prednisolone | 0.75 mg/kg/day (daily) | Off-label | Least expensive; first choice in many centers; intermittent dosing is inferior to daily (FOR-DMD trial, JAMA 2022) |
| Deflazacort (Emflaza) | 0.9 mg/kg/day | FDA-approved (DMD, ≥5 years) | Significantly less weight gain than prednisone; somewhat higher risk of cataracts (usually asymptomatic); level C evidence |
| Vamorolone (Agamree) | 6 mg/kg/day | FDA-approved (DMD, ≥2 years; October 2023) | First-in-class dissociative steroid; retains NF-κB inhibition but lacks bone-related side effect moiety; preserves linear growth and reduces bone turnover biomarkers; similar efficacy to prednisone at 24 and 48 weeks in RCTs |
Patients and families must be counseled about the side effects of chronic corticosteroid use, including weight gain, growth suppression, osteoporosis and fracture risk, behavioral problems, and adrenal suppression. Abrupt cessation must be avoided, and stress-dose steroids are required during fever, infection, and surgery to prevent adrenal crisis.
Givinostat (Duvyzat)
Givinostat is a pan-histone deacetylase (HDAC) inhibitor that represents the first nonsteroidal, non-variant-specific pharmacotherapy for DMD. FDA-approved in March 2024 for patients with DMD aged ≥6 years, it is used as add-on therapy to corticosteroids.
- Mechanism: Inhibits HDACs, reducing inflammatory infiltrate and fibrosis while increasing functional muscle tissue
- Phase 3 EPIDYS trial: Ambulatory boys on stable corticosteroids showed significantly less decline on the four-stair climb assessment and North Star Ambulatory Assessment (NSAA) at 72 weeks versus placebo
- Adverse effects: Diarrhea, vomiting, abdominal pain, thrombocytopenia, hypertriglyceridemia
- Monitoring: CBC, liver function tests, and serum triglycerides at regular intervals
- BMD trial: A separate phase 3 trial of givinostat in BMD failed to meet its primary endpoint (change in muscle fibrosis on MRI at 12 months)
Exon-Skipping Therapies
Exon skipping uses antisense oligonucleotides (ASOs) to bind specific sequences in the dystrophin pre-mRNA, causing the adjacent exon containing a frameshift variant to be spliced out. This restores the reading frame, theoretically converting a DMD phenotype toward a BMD phenotype by producing a truncated but partially functional dystrophin protein. All approved agents are phosphorodiamidate morpholino oligomers (PMOs) administered as weekly intravenous infusions.
| Agent | Target Exon | FDA Approval | Eligible Patients | Key Data |
|---|---|---|---|---|
| Eteplirsen (Exondys 51) | Exon 51 | 2016 (accelerated) | ~13% of DMD | PROMOVI: 7-fold increase in dystrophin from baseline; absolute expression remained very low (0.08% → 0.93% at 188 weeks); functional benefit debated |
| Golodirsen (Vyondys 53) | Exon 53 | 2019 (accelerated) | ~10% of DMD | Long-term functional outcomes at 3 years did not reach statistical significance (likely underpowered) |
| Viltolarsen (Viltepso) | Exon 53 | 2020 (accelerated) | ~10% of DMD | Statistically significant functional improvements at 24 and 109 weeks; stabilization of time-to-stand; confirmatory RACER53 trial did not meet primary endpoint |
| Casimersen (Amondys 45) | Exon 45 | 2021 (accelerated) | ~8% of DMD | Approval based on increased dystrophin expression; limited functional data |
Overall, approximately 30% of DMD patients are eligible for a currently approved exon-skipping therapy. While these agents appear safe, functional benefit has been variable and modest at best. Next-generation exon-skipping agents with improved cellular uptake are in development, including peptide-conjugated PMOs and endosomal escape vehicle (EEV) technology platforms.
Gene Therapy: Delandistrogene Moxeparvovec (Elevidys)
Gene therapy for DMD is limited by the fact that the full-length DMD cDNA (~14 kb) exceeds the packaging capacity of adeno-associated virus (AAV) vectors (~5 kb). This led to the development of shortened microdystrophin constructs, based on observations that patients with mild BMD carrying very large in-frame deletions (e.g., exons 17–48) remained ambulatory into their sixties.
Approval and Efficacy
- Delandistrogene moxeparvovec (Elevidys; SRP-9001) uses an AAVrh74 vector with an MHCK7 promoter to drive expression of microdystrophin in skeletal and cardiac muscle after a single IV infusion
- June 2023: Accelerated FDA approval for ambulatory boys aged 4–5 years
- June 2024: Full FDA approval in ambulatory boys (ages 4–5); accelerated approval extended to non-ambulatory patients based on microdystrophin expression as a biomarker
- Phase 2 data: 30–40% microdystrophin expression; stabilization of NSAA for up to 2 years post-treatment
- Phase 3 EMBARK trial: Did not meet its primary endpoint of NSAA improvement at 52 weeks; approval influenced by improvements in secondary measures and the lack of effective alternatives
Safety Concerns and Revised Labeling (2025)
Elevidys Safety Alert
- Two patient deaths in spring 2025 were attributed to acute liver failure in non-ambulatory boys following delandistrogene moxeparvovec infusion
- A third death occurred during a trial using the same AAV vector in a non-ambulatory patient with LGMD
- The FDA added a boxed warning for acute serious liver injury and acute liver failure
- The indication was restricted to ambulatory patients aged ≥4 years only
- Distribution for non-ambulatory use was suspended; dosing in ambulatory boys was briefly paused and then resumed
- Weekly liver function testing is required for ≥3 months post-infusion; patients must remain near an appropriate medical facility for 2 months after treatment
Eligibility and Contraindications
- Patients with deletions of exon 8 and/or exon 9 are ineligible (absolute contraindication)
- Variants in exons 1–17 or 59–71 may confer increased risk for immune-mediated myositis
- Significant preexisting cardiomyopathy is a relative contraindication, even in ambulatory patients
- Preexisting anti-AAV antibody titers must be checked (~86% of patients aged 4–18 are seronegative)
- Corticosteroid regimen must be standardized to prednisone/prednisolone 1 mg/kg/day before and after infusion (vamorolone and deflazacort were not studied in gene therapy trials)
Limitations
- Durability unknown: AAV vectors do not transduce satellite cells (muscle stem cells); the vector is likely diluted as stem cells proliferate during growth
- Single-use therapy: Redosing is expected to be unsafe and ineffective due to anti-AAV immune responses
- Theoretical risk: Integration of the gene therapy vector into the host genome (mutagenesis) has been reported only in animal models to date
Other Genetic Therapies
Stop-Codon Readthrough: Ataluren
Ataluren is an oral small molecule that induces ribosomal readthrough of premature stop codons, applicable to the ~10% of DMD patients with nonsense variants. It received conditional approval in Europe in 2014 but has not been FDA-approved. The phase 3 ACT-DMD trial failed its primary endpoint (6-minute walk test), though a long-term study showed a 2.2-year delay in loss of ambulation and 1.8-year delay in FVC decline below 60% predicted. The European Medicines Agency declined to renew conditional approval in early 2024, while the FDA accepted a resubmitted NDA in October 2024.
CRISPR/Cas9 Genome Editing
CRISPR-based editing aims to correct DMD variants directly, with the potential to restore full-length dystrophin expression—particularly relevant for BMD patients ineligible for microdystrophin therapy. However, a 27-year-old man with advanced DMD died of acute respiratory distress syndrome and cardiac arrest 8 days after treatment with an rAAV9-delivered CRISPR construct, underscoring the serious risks in patients with advanced disease and cardiac comorbidities.
Cardiac Management
Cardiomyopathy and arrhythmia are major sources of morbidity and mortality across all dystrophinopathies. The 2025 ACTION (Advanced Cardiac Therapies Improving Outcomes Network) consensus recommendations provide a standardized framework for cardiac care:
| Timing | Assessment | Intervention |
|---|---|---|
| At diagnosis | Baseline ECG + echocardiogram or cardiac MRI | Establish cardiology follow-up |
| Until age 10 | ECG + imaging every 1–2 years (or sooner if symptomatic) | Initiate ACE inhibitor or ARB by age 10 |
| After age 10 | Annual ECG + imaging (cardiac MRI preferred for fibrosis detection) | Add beta-blocker with onset of LV dysfunction; consider eplerenone as adjunctive therapy |
| Female carriers | Baseline ECG + cardiac MRI; follow-up frequency based on findings | Standard heart failure therapy if cardiomyopathy is detected |
Cardiac MRI is the most sensitive modality, detecting late gadolinium enhancement (a marker of myocardial fibrosis) before echocardiographic changes become apparent. Late gadolinium enhancement is an independent prognostic factor for DMD-related dilated cardiomyopathy. However, cardiac MRI may require sedation in younger boys.
Respiratory Management
Respiratory failure is a leading cause of death in DMD. Proactive monitoring and intervention can significantly prolong survival and improve quality of life:
- Pulmonary function testing: Forced vital capacity (FVC) monitored regularly; decline below 50% predicted indicates significant risk
- Nocturnal noninvasive ventilation (NIV): Initiated when symptoms of nocturnal hypoventilation develop or FVC falls below 50% predicted; bilevel positive airway pressure (BiPAP) is preferred
- Cough assist devices: Mechanical insufflation-exsufflation for airway clearance when peak cough flow declines
- Sleep studies: Regular polysomnography to detect early nocturnal hypoventilation
- Corticosteroid benefit: Chronic corticosteroid therapy helps preserve FVC and delays the need for ventilatory support
Orthopedic and Other Management
Orthopedic
- Scoliosis: Posterior spinal fusion is recommended for severe neuromuscular scoliosis, though the need has declined with early corticosteroid use
- Contractures: Physical therapy, stretching, and orthotic management; Achilles tendon release and ankle surgery generally do not improve mobility in ambulatory patients
- Fractures: Long bone fractures can prematurely curtail ambulation and carry a risk of potentially fatal fat emboli; regular DEXA scans, calcium/vitamin D supplementation, and bisphosphonates as appropriate
Endocrine
- Delayed puberty, growth suppression, and osteoporosis from chronic corticosteroid use require endocrine monitoring
- Weight management is critical in boys on corticosteroids
Gastrointestinal
- Progressive dysphagia may necessitate gastrostomy tube placement
- Gastroesophageal reflux is common with chronic steroid use
- Acute gastric dilation is a rare but serious complication due to gastric smooth muscle involvement
Neuropsychiatric
- Decreased dystrophin expression in the brain contributes to higher rates of intellectual disability, ADHD, anxiety, and depression
- Psychosocial support and pharmacotherapy for comorbid psychiatric conditions should be integrated into care
Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies (prevalence 5–12 per 100,000), caused by toxic gain of function of the transcription factor DUX4. Although genetically and mechanistically distinct from the dystrophinopathies, FSHD is an important differential diagnosis in the muscular dystrophy clinic.
Genetics
- FSHD1 (95% of cases): Autosomal dominant; contraction of the D4Z4 macrosatellite repeat array on chromosome 4q35 from the normal 8–100 repeats to 1–10 repeats, leading to hypomethylation and DUX4 derepression
- FSHD2 (5%): Digenic inheritance; hypomethylation without D4Z4 contraction, caused by variants in chromatin modifier genes (SMCHD1, DNMT3B, or LRIF1)
- Both types require the permissive 4qA haplotype containing a polyadenylation signal that stabilizes DUX4 mRNA
- D4Z4 repeat size is inversely proportional to severity: 1–6 repeats = more severe; 7–10 repeats = milder with higher nonpenetrance
- De novo variants account for 8–30% of cases; 20–30% of affected family members are nonpenetrant
Clinical Features
- Characteristic weakness pattern: Facial (orbicularis oculi/oris) → scapular stabilizers (winging, limited elevation) → upper arms ("Popeye arms" with preserved forearms) → trunk (positive Beevor sign) → tibialis anterior (foot drop)
- Poly-hill sign: Series of elevations along the upper back from selective muscle wasting
- Asymmetric weakness: A hallmark distinguishing FSHD from most other muscular dystrophies
- CK: Normal to 5× the upper limit of normal (unlike the massive elevations in dystrophinopathies)
- Lifespan: Not shortened, but ~20% of patients become wheelchair-dependent
- Extramuscular manifestations: Pain (>80%), fatigue (>60%), high-frequency hearing loss (15.5%), retinal vasculopathy (up to 25%), and rarely epilepsy or intellectual disability (more common in early-onset pediatric cases)
Diagnosis and Management
- Genetic testing: Southern blotting or optical genome mapping for D4Z4 repeat size and 4qA haplotype; FSHD is not captured by NGS panels
- FSHD2 workup: Methylation analysis of D4Z4 array followed by SMCHD1 sequencing if FSHD1 is excluded
- Current treatment: Supportive—physical therapy, orthotics (ankle-foot orthoses), NSAIDs for pain, scapular fixation surgery for severe winging; aerobic exercise and cognitive behavioral therapy for fatigue
- Losmapimod: A p38 MAPK inhibitor that decreased DUX4 expression in preclinical models; the phase 3 REACH trial (48 weeks, 260 patients) failed to meet its primary or secondary endpoints in September 2024, and the program was suspended
- Emerging therapies: RNA interference (AOC-1020, ARO-DUX4), CRISPR-based epigenetic editing (EPI-321), and myostatin inhibition (RO7204239) are in early-phase clinical trials
Multidisciplinary Care Model
Coordinated Multidisciplinary Approach
- Neuromuscular neurology: Diagnosis, treatment selection, care coordination, genetic counseling, and access to emerging therapies
- Cardiology: Baseline and serial cardiac surveillance; pharmacologic management of cardiomyopathy (ACEi/ARB, beta-blockers, eplerenone); carrier evaluation
- Pulmonology: Serial PFTs, sleep studies, cough assist devices, noninvasive ventilation
- Orthopedics/rehabilitation: Contracture management, scoliosis monitoring, adaptive equipment, mobility optimization
- Endocrinology: Growth monitoring, bone health (DEXA, calcium/vitamin D, bisphosphonates), puberty management
- Gastroenterology/nutrition: Weight management, dysphagia assessment, reflux treatment, gastrostomy tube when needed
- Neuropsychiatry/psychology: Neurodevelopmental assessment, psychosocial support, pharmacotherapy for ADHD, anxiety, and depression
- Genetic counseling: Family planning, carrier testing, prenatal counseling, newborn screening education
- The Muscular Dystrophy Association (MDA) multidisciplinary clinic model provides a coordinated framework for outpatient visits across all required specialties
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