High-level differentiator: If a patient remains ambulatory into late adolescence with a similar distribution of weakness, Becker muscular dystrophy is more likely.

Of note, many in the field have begun to consider DMD and BMD as dystrophinopathies that represent a spectrum of disease. This is partially because patients with genetic diagnoses of either DMD or BMD can have milder or more severe courses than what would be expected.

2. Duchenne vs. Limb-Girdle Muscular Dystrophies

Limb-girdle muscular dystrophy (LGMD) comprises a heterogeneous group of disorders affecting predominantly proximal muscles.

Key Differences:

• Inheritance: LGMD may be autosomal dominant or autosomal recessive; DMD is X-linked.
• Onset: LGMD varies widely, from childhood to adulthood.
• Distribution: Both cause proximal weakness, but LGMD often lacks early calf pseudohypertrophy.
• CK levels: Elevated in both, but often less extreme in LGMD.
• Cognitive involvement: Typically absent in LGMD.

High-level differentiator: A family history involving both sexes or an autosomal inheritance pattern should prompt consideration of LGMD over DMD.

3. Duchenne vs. Myotonic Dystrophy

Myotonic dystrophy differs fundamentally from Duchenne muscular dystrophy in both the pattern of weakness and systemic involvement.

Key Differences:

• Muscle involvement: Myotonic dystrophy typically presents with distal muscle weakness involving the hands, forearms, and lower legs. In DMD, predominantly affects proximal muscles, especially the pelvic girdle. In children with both diseases, hypotonia, developmental delay and facial weakness are common early symptoms.
• Myotonia: A hallmark of myotonic dystrophy is myotonia (delayed muscle relaxation), often evident as grip stiffness or difficulty releasing a handshake. This is not present in DMD.
• Onset: Myotonic dystrophy usually presents in adolescence or adulthood (although congenital forms exist), whereas DMD presents in early childhood.
• Systemic involvement: Myotonic dystrophy is a multisystem disorder commonly associated with cardiac conduction abnormalities, cataracts, endocrine dysfunction, and cognitive changes. DMD primarily affects skeletal and cardiac muscle, with some neurodevelopment involvement.
• Progression: Myotonic dystrophy often follows a slower, more variable course, while DMD is rapidly progressive with early loss of ambulation.

4. Duchenne vs. Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) presents with a distinct pattern of weakness.

Key Differences:

• Muscle involvement: FSHD prominently affects facial muscles (for example, inability to whistle or incomplete eye closure) though this may initially be subtle. Scapular winging may precede overt proximal arm weakness.
• Onset: Often adolescence or early adulthood.
• Progression: Slower and more variable.
• Lower limb involvement: Occurs later, unlike the early lower-limb weakness seen in DMD, often causing foot drop, which is not a common feature of DMD.

High-level differentiator: Facial weakness is not a feature of DMD; its presence should strongly suggest FSHD,

5. Duchenne vs. Congenital Muscular Dystrophies

Congenital muscular dystrophies present at or shortly after birth.

Key Differences:

• Onset: Neonatal hypotonia (“floppy infant”) in congenital forms versus delayed onset in DMD.
• Motor milestones: Often never fully achieved in congenital muscular dystrophies.
• Brain involvement: Structural brain abnormalities are more common.

High-level differentiator: Normal infancy followed by delayed milestones and progressive weakness favors DMD over congenital forms.

6. Duchenne vs. Emery–Dreifuss Muscular Dystrophy

Emery–Dreifuss muscular dystrophy has a distinct humeroperoneal distribution and characteristic early contractures that distinguish it from DMD.

Key Differences:

• Muscle involvement: Emery–Dreifuss typically affects humeral (upper arm) and peroneal (lower leg) muscles, whereas DMD primarily involves proximal muscles, especially the hips and thighs.
• Contractures: Early joint contractures involving the elbows, Achilles tendons, and posterior neck are a hallmark of Emery–Dreifuss and may precede significant weakness. In DMD, contractures occur later.
• Onset: Emery–Dreifuss often presents in late childhood to adolescence, compared with early childhood onset in DMD.
• Cardiac involvement: Emery–Dreifuss is strongly associated with cardiac conduction defects such as arrhythmias and heart block, often preceding and manifesting with more severity than skeletal muscle weakness. DMD more commonly causes dilated cardiomyopathy.
• Progression: Emery–Dreifuss generally progresses more slowly, with preservation of ambulation into adulthood, whereas DMD is rapidly progressive.

High-level differentiator: Early elbow or Achilles contractures with humeroperoneal weakness should prompt consideration of Emery–Dreifuss muscular dystrophy rather than Duchenne.

Why Different Muscular Dystrophies Affect Different Muscles

Although often grouped together, muscular dystrophies do not share a single mechanism. Only dystrophinopathies—such as Duchenne muscular dystrophy and Becker muscular dystrophy—result from loss of dystrophin. Other forms involve distinct proteins and cellular pathways, leading to selective patterns of muscle involvement.

Several factors explain this regional vulnerability:

• Protein function and localization: Different muscular dystrophies affect proteins with specialized roles such as membrane stability, nuclear structure, or RNA processing. These functions are not equally critical across all muscle groups.
• Mechanical stress: Muscles subjected to greater biomechanical load are more susceptible to injury when structural integrity is compromised. This helps explain early proximal weakness in dystrophinopathies and contracture-prone regions in disorders such as Emery–Dreifuss muscular dystrophy.
• Muscle fiber composition: Variations in type I (slow-twitch) and type II (fast-twitch) fiber distribution influence susceptibility, as certain diseases preferentially affect specific fiber types.
• Regenerative capacity: Muscle groups differ in their ability to repair damage. Limited regenerative reserve may contribute to early involvement of specific regions, such as facial muscles in FSHD.
• Gene expression patterns: Disease-related genes may be differentially expressed across muscle groups, contributing to characteristic distributions of weakness.

Clinical Implication

Recognizing the pattern of muscle involvement is central to diagnosis. Distinct distributions—proximal, distal, facial-scapular, or humeroperoneal—reflect the underlying biology and can guide targeted evaluation.

Summary Evaluation Steps

1. Serum CK measurement (initial screening)
2. Genetic testing (multiplex ligation-dependent probe amplification or sequencing)
3. Cardiac evaluation (baseline echocardiogram or cardiac MRI)
4. Pulmonary function testing (age-appropriate)

Muscle biopsy is now generally reserved for atypical or inconclusive cases. Increasingly, diagnosis occurs through family screening, incidental hyperCKemia, or newborn screening initiatives are gaining momentum.

References

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