U01.01.051 Muscular dystrophies

Muscular dystrophies are genetic disorders characterized by progressive muscle weakness and wasting. Key subtypes include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and Myotonic dystrophy.

Duchenne Muscular Dystrophy (DMD)

Etiology and Pathophysiology

Inheritance: X-linked recessive
Mutation: Frameshift or nonsense mutations in the dystrophin (DMD) gene, leading to truncated or absent dystrophin protein.
Protein Function: Dystrophin anchors the cytoskeleton (actin) of muscle cells to transmembrane proteins (α- and β-dystroglycan) that interact with the extracellular matrix. Loss of dystrophin causes myonecrosis and progressive muscle damage.

Clinical Features

Onset: Before 5 years of age
Progression:
- Weakness begins in pelvic girdle muscles and progresses superiorly.
- Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle.
- Waddling gait and lordosis.
Gower’s Sign: Difficulty rising to a standing position; patient uses upper extremities for support.
Cardiac Complications: Dilated cardiomyopathy, a common cause of death.

Diagnosis

Laboratory Findings:
- Elevated creatine kinase (CK) and aldolase.
Confirmation: Genetic testing.

Key Features of Duchenne Muscular Dystrophy	Description
Mutation	Frameshift/nonsense mutation
Dystrophin Protein	Absent or truncated
Onset	Before 5 years of age
Clinical Signs	Gower’s sign, waddling gait, pseudohypertrophy of calves
Cause of Death	Dilated cardiomyopathy

Becker Muscular Dystrophy (BMD)

Etiology and Pathophysiology

Inheritance: X-linked recessive.
Mutation: Non-frameshift deletions in the dystrophin (DMD) gene, leading to partially functional dystrophin.

Clinical Features

Onset: Adolescence or early adulthood.
Severity: Less severe than Duchenne (Becker is “better”).

Diagnosis

Genetic testing confirms the diagnosis.

Key Features of Becker Muscular Dystrophy	Description
Mutation	Non-frameshift deletion
Dystrophin Protein	Partially functional
Onset	Adolescence/early adulthood
Clinical Signs	Similar but milder than Duchenne

Myotonic Dystrophy

Etiology and Pathophysiology

Inheritance: Autosomal dominant.
Mutation: CTG trinucleotide repeat expansion in the DMPK gene, causing abnormal expression of myotonin protein kinase.

Clinical Features

Myotonia: Difficulty relaxing muscles (e.g., delayed release of hand after handshake).
Muscle Wasting: Progressive.
Additional Manifestations:
- Cataracts
- Frontal balding (early balding in men, “toupee”)
- Testicular atrophy
- Arrhythmias

Key Features of Myotonic Dystrophy	Description
Mutation	CTG trinucleotide repeat
Clinical Signs	Myotonia, cataracts, balding, gonadal atrophy
Other Complications	Arrhythmias

Points to Remember

Duchenne Muscular Dystrophy
- Most severe, early onset (before 5 years).
- Pseudohypertrophy of calves and Gower’s sign are hallmark features.
Becker Muscular Dystrophy
- Less severe, later onset (adolescence to early adulthood).
- Retains some dystrophin function.
Myotonic Dystrophy
- Autosomal dominant inheritance.
- CTG repeat expansion leads to systemic features like cataracts, balding, and gonadal atrophy.

Mnemonic for Myotonic Dystrophy

C: Cataracts
T: Toupee (frontal balding)
G: Gonadal atrophy

Bibliography

Harrison’s Principles of Internal Medicine, 21st Edition.
Robbins and Cotran Pathologic Basis of Disease, 10th Edition.
UpToDate – Overview of Muscular Dystrophies.

USMLE Step 1 Review Series

Curriculum

U01.01.051 Muscular dystrophies

Duchenne Muscular Dystrophy (DMD)

Etiology and Pathophysiology

Clinical Features

Diagnosis

Becker Muscular Dystrophy (BMD)

Etiology and Pathophysiology

Clinical Features

Diagnosis

Myotonic Dystrophy

Etiology and Pathophysiology

Clinical Features

Points to Remember

Mnemonic for Myotonic Dystrophy

Bibliography

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