Duchenne Muscular Dystrophy (DMD): Case Discussion & Key Points
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 5 years, Gender: Male, Informant: Mother (Reliable)
Chief Complaints
- Difficulty walking and frequent falls – 1 year
- Inability to climb stairs and rise from the floor without support – 6 months
- Enlargement of both calves – noticed since 3 years of age
History Summary
The child sat at 8 months and walked at 16 months (delayed). Since the age of 4 years, parents noticed he falls frequently while walking, has a waddling gait, and cannot run as fast as peers. He uses his hands to push himself up from the floor. He has difficulty climbing stairs and needs to hold the railing with both hands. He tires easily. No cyanosis, no sensory complaints, no sphincter disturbance. He attends school but is reportedly a slow learner; no convulsions. He was born full-term by NVD, cried immediately. No similar illness in siblings or family. Parents are non-consanguineous.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Weight | 16 kg (10th centile) | Mildly below average |
| Height | 105 cm (25th centile) | Normal |
| Gait | Waddling (Trendelenburg) | Proximal hip muscle weakness |
| Gower's Sign | Positive | Proximal lower limb + trunk weakness |
| Calf muscles | Bilaterally enlarged, firm | Pseudohypertrophy |
| Muscle power | 3/5 proximally (hip, shoulder), 4/5 distally | Proximal > distal weakness |
| Deep tendon reflexes | Absent knee jerks, reduced ankle jerks | Lost with muscle replacement |
| Sensation | Intact | Pure motor disorder (no neuropathy) |
| Spine | No scoliosis (early case) | — |
| Cardiorespiratory | Normal at this stage | Dilated CMP appears later |
Cognitive: Mild learning difficulty noted (IQ mildly reduced). Facial muscles normal. No cranial nerve involvement. No fasciculations or sensory level.
✅ Complete Diagnosis
Duchenne Muscular Dystrophy — X-linked recessive dystrophinopathy presenting with progressive proximal muscle weakness, pseudohypertrophy of calves, positive Gower's sign, and waddling gait in a 5-year-old male. Currently ambulatory (early phase).
📝 History — Exam Q&A
DMD is the most common and most severe form of muscular dystrophy. It is an X-linked recessive disorder caused by mutations in the DMD gene (Xp21.2) leading to absent or severely reduced dystrophin protein, resulting in progressive muscle fiber degeneration and weakness.
- Incidence: ~1 in 3,500–5,000 live male births
- Most common hereditary neuromuscular disease in children
- Affects males almost exclusively; females are usually carriers
- Delayed motor milestones (late walking, average ~15–16 months)
- Frequent falls and difficulty running
- Difficulty climbing stairs
- Difficulty rising from the floor (Gower's maneuver)
- Waddling gait and toe walking
- Enlarged calf muscles (noticed by parents as "well-built legs")
- Easy fatigability
- Mild cognitive/learning difficulties (in ~30%)
💡 Pearl
Symptoms typically become noticeable between 3–5 years of age. The child is often normal at birth; no abnormality noted until ambulation is established.
X-linked recessive inheritance.
- Carrier mother (XdX) × Normal father (XY) → 50% of sons affected, 50% of daughters carriers
- ~2/3 of cases are inherited from carrier mothers
- ~1/3 of cases represent de novo mutations (new mutations with no family history)
- Females are carriers and usually unaffected; ~2.5–20% of carriers may have mild myopathic features (manifesting carriers)
- Carrier females should be screened for cardiomyopathy
| Milestone | Normal Age | DMD Pattern |
|---|---|---|
| Sitting | 6–9 months | Normal or mildly delayed |
| Walking independently | 12–15 months | Delayed (15–18 months) |
| Climbing stairs | ~18–24 months | Difficulty noted early |
| Running | 2 years | Slow, abnormal |
| Speech | Normal | Usually normal; expressive language may lag |
Also ask about: school performance, learning difficulties, and behavioral issues (as dystrophin is present in the brain).
- No sensory complaints — rules out peripheral neuropathy (e.g., GBS, CMT)
- No sphincter disturbance — rules out spinal cord disease
- No fasciculations — rules out anterior horn cell disease (SMA)
- No facial or bulbar weakness — helps differentiate from myotonic dystrophy, facioscapulohumeral MD
- No consanguinity — X-linked disorders don't usually require consanguinity but autosomal forms do
- No regression of milestones previously achieved — suggests metabolic/degenerative cause if present
| Age | Clinical Status |
|---|---|
| 0–2 years | Often normal; CK elevated from birth; mild motor delays |
| 3–5 years | Waddling gait, Gower's sign, toe walking, frequent falls |
| 5–10 years | Progressive weakness; difficulty climbing stairs, rising |
| 10–12 years | Loss of ambulation; wheelchair dependent |
| Teens | Scoliosis, respiratory muscle weakness, dilated cardiomyopathy |
| Late teens–20s | Respiratory failure, cardiac failure — death (historically in early 20s; now extended to 30s+ with treatment) |
The DMD gene is located at Xp21.2 and contains 79 exons. It is the largest known human gene (~2.4 Mb). It encodes dystrophin, a 427-kDa cytoskeletal protein that stabilizes the muscle cell membrane (sarcolemma) against mechanical stress during contraction.
- ~60–70%: Large intragenic deletions (most common); cause frameshift → non-functional/absent dystrophin
- ~10%: Duplications
- ~25–30%: Point mutations (nonsense, splice site)
- Hotspot region: Exons 45–53 (most common deletion site); also exons 2–22
💡 Frame-shift Rule (Monaco's Rule)
Out-of-frame (frameshift) mutations → DMD (absent dystrophin). In-frame mutations → BMD (truncated but partially functional dystrophin). This is the basis of exon-skipping therapy — converting DMD-type out-of-frame mutations to BMD-type in-frame mutations.
| Feature | DMD | BMD |
|---|---|---|
| Gene/Locus | DMD gene, Xp21.2 | Same DMD gene, Xp21.2 |
| Mutation type | Out-of-frame (frameshift) | In-frame |
| Dystrophin | Absent | Reduced/truncated (partially functional) |
| Age of onset | 2–5 years | 5–15 years (later) |
| Loss of ambulation | Before age 13 | After age 16 (or never) |
| CK levels | Very high (50–100× normal) | High (5–20× normal) |
| Severity | Severe, rapidly progressive | Milder, slower |
| Life expectancy | ~20s–30s | 4th–5th decade |
🩺 Examination — Exam Q&A
Gower's sign is the classic maneuver by which a child with proximal lower limb and trunk muscle weakness rises from the floor.
Steps of Gower's maneuver:
- Child rolls to prone position
- Pushes up onto all four limbs
- Walks hands up the legs (thighs) toward knees, then thighs, to compensate for weak hip extensors
- Finally achieves upright posture
Significance: Indicates weakness of hip extensors, glutei, and paraspinal muscles. Seen in DMD, SMA, polymyositis, and other myopathies.
💡 Pearl
To elicit: Ask the child to sit on the floor, then ask him to get up. Watch carefully — do NOT demonstrate to the child first as this may influence the maneuver.
Pseudohypertrophy refers to apparent enlargement of muscles due to replacement of muscle fibers by fat and fibrous connective tissue, not due to actual muscle hypertrophy.
Most commonly affected: Calf muscles (gastrocnemius) — bilateral, firm, rubbery consistency, non-tender.
Other muscles: Deltoid, infraspinati, vastus lateralis, glutei may also show pseudohypertrophy.
Pathological basis: Repeated cycles of muscle necrosis and regeneration lead to replacement by fat and fibrous tissue → increased bulk without functional strength.
Waddling (Trendelenburg) gait: The child lurches side to side with each step, with exaggerated lumbar lordosis and protruding abdomen.
Why waddling: Weakness of the gluteus medius (hip abductor) means the pelvis drops to the opposite side during the swing phase. The child compensates by leaning the trunk over the stance leg → characteristic lateral sway.
Additionally, toe walking (equinus gait) is common due to calf tightness and hip flexor/extensor imbalance.
Proximal > Distal weakness is the hallmark. Lower limbs are affected before upper limbs.
Earliest muscles affected: Hip extensors (glutei), hip flexors, and quadriceps.
Sequence of involvement:
- Hip girdle (glutei, quadriceps) → waddling, Gower's sign
- Shoulder girdle (deltoid, pectorals) → difficulty raising arms overhead
- Neck flexors (chin-on-chest test weak)
- Respiratory muscles (intercostals, diaphragm) → restrictive lung disease
- Cardiac muscle → dilated cardiomyopathy
Relatively spared (even in advanced disease): Sartorius, gracilis, semitendinosus, tibialis posterior, ocular muscles, sphincters.
Deep tendon reflexes are diminished or absent in affected muscles, corresponding to the degree of muscle involvement:
- Knee jerks (L3–L4): Absent early (quadriceps affected early)
- Ankle jerks: Reduced then absent later
- Biceps/Triceps: Preserved early, lost later as upper limbs are affected
Reflexes are lost due to muscle (efferent) destruction — NOT due to nerve disease. Sensation is always normal in DMD — this is a key distinguishing feature from neuropathies.
Meryon's sign (Scapular winging / Slipping through the hands): When the examiner holds the child under the axillae and lifts him, the child slips through the hands because the shoulder girdle muscles (serratus anterior, trapezius, pectorals) are weak and cannot brace the shoulder joint.
Significance: Indicates shoulder girdle muscle weakness. This is also the mechanism behind scapular winging seen in DMD.
Cardiac (appears from ~10 years):
- Tachycardia
- Displaced apex (cardiomegaly from dilated cardiomyopathy)
- S3 gallop, mitral regurgitation murmur (in advanced cases)
- Signs of heart failure (hepatomegaly, edema)
Respiratory (teens and beyond):
- Reduced chest expansion
- Paradoxical breathing (diaphragm weakness)
- Kyphoscoliosis (contributes to restrictive lung disease)
- Crepitations (recurrent infections, aspiration)
🚨 Important
Virtually all DMD patients develop dilated cardiomyopathy by their teens. Cardiac involvement is often subclinical early on but becomes a major cause of death.
| Feature | DMD | SMA (Type III, Kugelberg-Welander) |
|---|---|---|
| Fasciculations | Absent | Present (tongue, limbs) |
| Pseudohypertrophy | Present (calves) | Absent |
| Sensory | Normal | Normal |
| DTRs | Absent in affected muscles | Absent (lower motor neuron) |
| EMG | Myopathic | Neurogenic (fibrillations, large MUPs) |
| CK | Very high (50–100×) | Normal or mildly elevated |
| Gene | DMD (Xp21) | SMN1 (5q) |
| Sex | Males only (X-linked) | Both sexes (autosomal recessive) |
Vignos Scale (for lower limb function):
| Grade | Functional Status |
|---|---|
| 1 | Walks and climbs stairs without assistance |
| 2 | Walks and climbs stairs with aid of railing |
| 3 | Walks and climbs stairs slowly (>12 sec for 4 standard stairs) |
| 4 | Walks unassisted and rises from chair, cannot climb stairs |
| 5 | Walks unassisted but cannot rise from chair or climb stairs |
| 6 | Walks only with assistance or with braces |
| 7 | In wheelchair; sits erect and can perform ADLs |
| 8 | In wheelchair; sits erect; limited ADLs |
| 9 | In wheelchair; cannot sit erect without support |
| 10 | Confined to bed |
Other tools: North Star Ambulatory Assessment (NSAA) — used in clinical trials to measure motor function in ambulant DMD patients.
🔬 Investigations — Exam Q&A
Serum Creatine Kinase (CK) — also called CPK.
- In DMD: CK is elevated 50–100 times normal (may be >20,000 IU/L; normal <200 IU/L)
- CK is elevated from birth (even before symptoms), as muscle is already being damaged
- CK is highest in early disease; paradoxically falls in later stages as muscle mass is replaced by fat/fibrosis and there is less muscle to release CK
💡 Pearl
If a boy presents with unexplained elevated transaminases (AST/ALT), always check CK — the elevated "liver enzymes" may actually be of muscle origin, and DMD could be the underlying cause. This is a common diagnostic pitfall.
Genetic testing — Multiplex Ligation-Dependent Probe Amplification (MLPA) from peripheral blood leukocyte DNA is the primary confirmatory test. It detects deletions and duplications in the dystrophin gene (detects ~70–80% of mutations).
If MLPA is negative but DMD still suspected: Full sequencing of the DMD gene (Next-Generation Sequencing/NGS) to detect point mutations.
Older method (still asked in exams): Muscle biopsy with immunohistochemistry and immunofluorescence for dystrophin — shows absent or markedly reduced dystrophin staining.
Histopathology (H&E staining):
- Marked variation in muscle fiber size (fiber size variability)
- Necrotic fibers with phagocytosis
- Regenerating fibers (internalized nuclei, basophilic cytoplasm)
- Endomysial and perimysial fibrosis
- Replacement by fat cells (adipocytes)
- No fiber type grouping (distinguishes from neurogenic atrophy)
Immunohistochemistry (most important):
- DMD: Absent dystrophin staining at the sarcolemma
- BMD: Reduced/patchy dystrophin staining
EMG shows a myopathic pattern:
- Short duration, low amplitude motor unit action potentials (MUAPs)
- Early recruitment — many motor units fire at low force (because each motor unit is weak)
- No fibrillations (no denervation) — distinguishes from neuropathy
- Normal nerve conduction studies (NCS) — pure myopathy
💡 Memory Aid
Myopathy → Small MUAPs, Early Recruitment | Neuropathy → Large MUAPs, Reduced Recruitment, Fibrillations
Cardiac:
- ECG: Tall R waves in V1 (posterobasal fibrosis), deep Q waves in lateral leads, sinus tachycardia, right bundle branch block
- Echocardiography: Dilated cardiomyopathy — reduced LVEF, LV dilatation, posterior wall motion abnormalities — should be done at diagnosis, then every 2 years until age 10, then annually
- Holter monitoring for arrhythmias
Pulmonary:
- Pulmonary Function Tests (PFTs): Restrictive pattern — reduced FVC, FEV1, FEV1/FVC normal or increased, reduced total lung capacity
- Sleep study (polysomnography) for nocturnal hypoventilation
- Peak cough flow — assesses cough effectiveness
Due to muscle cell membrane damage and leakage of intracellular contents, the following are elevated:
- CK (Creatine Kinase): 50–100× normal — hallmark finding
- Aldolase: Elevated (glycolytic enzyme in muscle)
- LDH (Lactate Dehydrogenase): Elevated
- AST, ALT: Mildly elevated (isoforms present in muscle) — NOT a sign of liver disease
- Myoglobin: Elevated in blood and urine (myoglobinuria may cause dark urine)
Muscle MRI (T1 and STIR sequences) is increasingly used in DMD:
- Shows fatty infiltration of muscles as T1 hyperintensity
- STIR hyperintensity indicates active muscle inflammation/edema
- Helps document pattern of muscle involvement — particularly sparing of certain muscles (sartorius, gracilis)
- Used to monitor disease progression and response to therapy
- Guides muscle biopsy site selection to avoid end-stage muscle
Whole-body MRI protocols are used in research settings for comprehensive muscle mapping.
💊 Management — Exam Q&A
Corticosteroids are the cornerstone of DMD management — currently the only treatment proven to slow disease progression.
- Prednisolone: 0.75 mg/kg/day (daily) or 10 mg/kg/weekend (intermittent dosing)
- Deflazacort: 0.9 mg/kg/day — preferred in some centers due to less weight gain; FDA-approved for DMD ≥2 years
- Vamorolone: Newer dissociative steroidal anti-inflammatory drug with fewer side effects; approved for DMD ≥2 years
Benefits: Prolongs ambulation by 2–5 years, delays scoliosis, delays respiratory decline, may delay cardiomyopathy onset.
Side effects: Weight gain, short stature, delayed puberty, osteoporosis, cataracts, adrenal insufficiency, behavioral changes.
When to start: During the plateau phase of motor function (usually 4–8 years), before the child begins to decline — NOT in the gaining phase and NOT after ambulation is lost (debated).
| Domain | Management |
|---|---|
| Neuromuscular | Corticosteroids, genetic therapy, monitoring progression |
| Cardiac | ACE inhibitors/ARBs (from age 10 or at onset of dysfunction), beta-blockers, SGLT2 inhibitors; Echo monitoring |
| Respiratory | PFTs monitoring, nocturnal BiPAP when FVC <50%, cough assist device, flu/pneumococcal vaccination |
| Orthopedic | Ankle-foot orthoses (AFOs) for equinus, surgical correction of scoliosis (spinal fusion when FVC >50%) |
| Physiotherapy | Passive stretching (prevent contractures), hydrotherapy, standing frames |
| Nutrition | Avoid obesity (corticosteroid side effect), calcium + Vitamin D supplementation (for bone health) |
| Psychosocial | Neuropsychological assessment, learning support, family counseling |
| Genetic counseling | Carrier detection, prenatal diagnosis for family members |
- Non-invasive ventilation (NIV/BiPAP):
- FVC <50% predicted, OR
- Nocturnal hypoventilation (SpO2 <95% on sleep study), OR
- Morning headache, daytime somnolence (signs of CO2 retention)
- Cough Assist Device (Mechanical In-Exsufflation): When peak cough flow <160–270 L/min — unable to clear secretions effectively
- Tracheostomy + invasive ventilation: In end-stage respiratory failure or when NIV fails (family decision)
- ACE inhibitors (Enalapril, Lisinopril): Start at age 10 years (even if echo normal) to delay cardiomyopathy progression, OR start at any age when LVEF falls below normal
- ARBs (Losartan): If ACE inhibitor not tolerated
- Beta-blockers (Carvedilol): Added when LVEF is reduced
- Aldosterone antagonists (Spironolactone/Eplerenone)
- SGLT-2 inhibitors: Emerging evidence for cardioprotection in DMD
- Corticosteroids may delay onset of cardiomyopathy
1. Joint Contractures:
- Most common at: Ankle (equinus), hip flexors, knee flexors, iliotibial band
- Management: Daily passive stretching, AFOs (ankle-foot orthoses), nocturnal splints, surgical tenotomy in selected cases
2. Scoliosis:
- Develops rapidly after loss of ambulation (from unbalanced trunk muscle weakness)
- Corticosteroids delay onset
- Spinal fusion surgery (posterior instrumented fusion) indicated when:
- Cobb angle >20–25° and progressing, AND
- FVC >50% predicted (to tolerate surgery)
3. Fractures: Risk increased by corticosteroid-induced osteoporosis. Give calcium (500–1000 mg/day) + Vitamin D (400–800 IU/day). Bisphosphonates for significant osteoporosis.
🚨 Anesthesia Risk in DMD
DMD patients are at high risk of malignant hyperthermia-like reactions and life-threatening rhabdomyolysis with hyperkalemic cardiac arrest when given:
- Succinylcholine — ABSOLUTELY CONTRAINDICATED
- Volatile anesthetic agents (halothane, isoflurane, desflurane) — use with caution
Preferred approach: Total intravenous anesthesia (TIVA) with propofol. Preoperative cardiac and respiratory evaluation mandatory. The anesthesiologist must always be informed of the diagnosis.
- Carrier testing: All maternal female relatives (sisters, maternal aunts) should be offered genetic testing
- Prenatal diagnosis: Chorionic villus sampling (CVS) at 10–12 weeks or amniocentesis at 16–18 weeks for at-risk pregnancies
- Preimplantation genetic diagnosis (PGD): For IVF-conceived embryos; embryos tested before uterine transfer
- Recurrence risk: For carrier mother: 50% chance of affected sons, 50% of daughters are carriers
- Explain that ~1/3 of cases are de novo mutations; normal CK in mother does not exclude carrier status (use molecular testing)
🔭 Recent Advances — Exam Q&A
Principle: Antisense oligonucleotides (ASOs) are used to "skip" specific exons during pre-mRNA splicing. This converts an out-of-frame (DMD-type) mutation into an in-frame (BMD-type) mutation, allowing production of a shorter but partially functional dystrophin protein.
Goal: Convert DMD phenotype → BMD phenotype.
FDA-approved exon-skipping drugs:
| Drug | Target Exon | Mutation Amenable | Approval |
|---|---|---|---|
| Eteplirsen (Exondys 51) | Exon 51 | ~13% of DMD patients | FDA 2016 |
| Golodirsen (Vyondys 53) | Exon 53 | ~8% of DMD patients | FDA 2019 |
| Viltolarsen (Viltepso) | Exon 53 | ~8% of DMD patients | FDA 2020 |
| Casimersen (Amondys 45) | Exon 45 | ~8% of DMD patients | FDA 2021 |
Limitation: Mutation-specific — applicable only to patients with mutations in the relevant exon hotspot region (exons 43–55). Not universally applicable.
Gene therapy uses an adeno-associated virus (AAV) vector to deliver a modified, shortened version of the dystrophin gene into muscle cells — called micro-dystrophin.
The dystrophin gene is too large (~2.4 Mb) to fit in an AAV vector. Scientists created a truncated version that retains the essential functional domains (N-terminal actin-binding domain and cysteine-rich domain) — producing a shorter protein that partially restores muscle membrane function.
Delandistrogene moxeparvovec (Elevidys; SRP-9001):
- FDA approved June 2023 for ambulatory DMD patients ≥4 years with confirmed DMD gene mutation
- Single intravenous dose
- Produces micro-dystrophin in skeletal and cardiac muscle
- Goal: Slow disease progression, not a cure
- Side effects: Hepatitis, myositis, thrombocytopenia, rhabdomyolysis — require monitoring
💡 Key Concept
Gene therapy aims to convert DMD into a "BMD-like" condition. It is not curative but represents the most disease-modifying approach currently available.
Applicable to patients with DMD caused by nonsense mutations (premature stop codons), which account for ~10–15% of DMD cases.
Ataluren (Translarna; PTC124):
- An oral drug that promotes ribosomal read-through of premature stop codons, allowing a full-length dystrophin to be produced
- Was approved conditionally in Europe (EMA) for ambulatory DMD patients ≥2 years with nonsense mutations; however, the EU conditional marketing authorization was not renewed in March 2025 after the EMA concluded that effectiveness could not be confirmed
- Not FDA-approved in the USA
Vamorolone (Agamree) is a dissociative steroidal anti-inflammatory — a modified corticosteroid that retains anti-inflammatory effects while dissociating from many of the adverse effects of traditional corticosteroids.
FDA approved for DMD patients ≥2 years.
Advantages over prednisolone/deflazacort:
- Less growth suppression
- Less bone loss and adrenal suppression
- Less weight gain
- Improved side-effect profile while maintaining efficacy in slowing disease progression
CRISPR-Cas9 technology is being explored to permanently correct or delete the problematic exon from the DMD gene in muscle cells, restoring the reading frame.
Approaches under investigation:
- Exon deletion using two guide RNAs flanking the mutated exon
- Direct correction of the mutated sequence (more challenging)
Limitations/Challenges:
- Delivery to all muscle cells throughout the body is technically very difficult
- Off-target mutagenesis risk
- Immune response to Cas9 protein
- Currently preclinical/early-phase trials only
- Not yet approved for clinical use
DMD newborn screening involves measuring CK levels from the routine newborn blood spot (Guthrie card). If elevated, confirmatory genetic testing is done.
Advantage: Diagnosis in the pre-symptomatic phase allows:
- Earlier initiation of corticosteroids and emerging gene/exon-skipping therapies (before irreversible muscle loss)
- Genetic counseling and carrier testing for the family
- Avoidance of anesthetic risk (succinylcholine) in unsuspected cases undergoing surgery
Currently, newborn screening for DMD is available in some countries (China, parts of USA) but is not yet universally implemented.
⚡ Key Points — Quick Revision
One-Liners for Exam
- Most common muscular dystrophy: DMD (most common hereditary neuromuscular disease)
- Inheritance: X-linked recessive; gene at Xp21.2; 79 exons; encodes dystrophin
- Protein: Dystrophin — absent in DMD, truncated in BMD
- Most common mutation: Out-of-frame deletions (60–70%), hotspot exons 45–53
- Frame-shift rule: Out-of-frame → DMD; In-frame → BMD (Monaco's rule)
- Presentation age: 3–5 years (symptoms first apparent)
- Gower's sign: "Walking up on oneself" — proximal lower limb and trunk weakness
- Pseudohypertrophy: Calves most common — fat + fibrous tissue replacement, NOT true muscle hypertrophy
- Gait: Waddling (Trendelenburg) + toe walking
- First investigation: Serum CK (50–100× normal; elevated from birth)
- Gold standard diagnosis: MLPA genetic testing (then full gene sequencing if MLPA negative)
- Muscle biopsy: Absent dystrophin on immunohistochemistry; fiber necrosis, fibrosis, fat replacement
- EMG: Myopathic — short, low amplitude MUAPs; early recruitment; normal NCS
- Loss of ambulation: ~age 10–12 years
- Cardiac complication: Dilated cardiomyopathy (virtually all patients by teens)
- Respiratory complication: Restrictive lung disease → nocturnal hypoventilation → respiratory failure
- Pharmacological Rx: Prednisolone 0.75 mg/kg/day or Deflazacort — slows progression, prolongs ambulation
- Anesthesia: ABSOLUTELY avoid succinylcholine (risk of hyperkalemic cardiac arrest)
- Exon skipping: Eteplirsen (exon 51), Golodirsen/Viltolarsen (exon 53), Casimersen (exon 45)
- Gene therapy: Delandistrogene moxeparvovec (FDA 2023) — delivers micro-dystrophin via AAV
- Death: Respiratory failure or cardiomyopathy (historically ~20s; now 30s+ with multidisciplinary care)
- Vamorolone: Newer steroid with better side-effect profile (FDA approved)
- Maladie de Roger equivalent in DMD: No spontaneous remission — DMD is relentlessly progressive
⚡ Comparison: DMD vs SMA vs Myotonic Dystrophy
| Feature | DMD | SMA (Type III) | Myotonic Dystrophy |
|---|---|---|---|
| Inheritance | X-linked recessive | Autosomal recessive | Autosomal dominant |
| Gene | DMD (Xp21) | SMN1 (5q) | DMPK (19q) |
| Weakness pattern | Proximal > distal | Proximal > distal | Distal > proximal |
| Pseudohypertrophy | Yes (calves) | No | No |
| Fasciculations | No | Yes | No |
| Myotonia | No | No | Yes (grip myotonia) |
| CK | Very high | Normal/mildly raised | Mildly raised |
| Cardiac | Dilated CMP | Usually normal | Arrhythmias, conduction |