Muscular Dystrophy

A group of inherited genetic disorders causing progressive muscle weakness and degeneration

Table of Contents

Overview

Muscular dystrophy (MD) refers to a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. These disorders vary in age of onset, severity, and pattern of affected muscles. All forms of muscular dystrophy grow worse as muscles progressively degenerate and weaken, eventually leading to loss of mobility.

The different types of muscular dystrophy are caused by mutations in genes that encode proteins necessary for normal muscle function. The most common form, Duchenne muscular dystrophy (DMD), affects approximately 1 in 3,500 male births worldwide. Other major types include Becker, myotonic, facioscapulohumeral, and limb-girdle muscular dystrophies, each with distinct genetic causes and clinical presentations.

While there is currently no cure for muscular dystrophy, treatments can help manage symptoms, improve quality of life, and slow disease progression. Research continues to advance our understanding of these conditions, with promising therapies in development including gene therapy, exon skipping, and novel pharmaceutical approaches targeting the underlying genetic defects.

Symptoms

The symptoms of muscular dystrophy vary depending on the type and severity of the condition. Progressive muscle weakness is the primary symptom, but the pattern and rate of progression differ significantly between types. Symptoms typically worsen over time, though the rate of progression varies.

Common Early Symptoms

  • Progressive muscle weakness, often starting in specific muscle groups
  • Fatigue - excessive tiredness with minimal exertion
  • Frequent falls and difficulty with balance
  • Difficulty rising from sitting or lying positions
  • Waddling gait or walking on toes
  • Enlarged calf muscles (pseudohypertrophy)

Associated Symptoms

  • Hip pain - due to muscle weakness and altered gait
  • Joint contractures and limited range of motion
  • Scoliosis (curvature of the spine)
  • Respiratory difficulties as breathing muscles weaken
  • Feeling cold - due to reduced muscle mass and activity
  • Learning disabilities (in some types, particularly DMD)

Type-Specific Symptoms

  • Duchenne MD: Early childhood onset, rapid progression, wheelchair use by age 12
  • Becker MD: Later onset, slower progression, milder symptoms
  • Myotonic MD: Muscle stiffness (myotonia), cataracts, heart problems
  • Facioscapulohumeral MD: Facial muscle weakness, shoulder blade winging
  • Limb-girdle MD: Hip and shoulder weakness, variable progression

Causes

Muscular dystrophy is caused by mutations in genes responsible for the structure and function of muscle fibers. These genetic defects lead to the absence or dysfunction of critical muscle proteins, resulting in progressive muscle damage and weakness.

Genetic Basis

Different types of muscular dystrophy are caused by mutations in different genes. The most well-understood is Duchenne muscular dystrophy, caused by mutations in the DMD gene that encodes dystrophin, a protein essential for maintaining muscle fiber integrity. Without functional dystrophin, muscle fibers are easily damaged during normal use.

Major Genetic Causes by Type

  • Duchenne/Becker MD: Mutations in the dystrophin gene (DMD) on the X chromosome
  • Myotonic dystrophy: Expanded CTG repeat in the DMPK gene (type 1) or CCTG repeat in the CNBP gene (type 2)
  • Facioscapulohumeral MD: Deletion of DNA repeats on chromosome 4
  • Limb-girdle MD: Mutations in various genes encoding sarcoglycan proteins and other muscle proteins
  • Emery-Dreifuss MD: Mutations in emerin or lamin A/C genes

Inheritance Patterns

X-linked Recessive

Duchenne and Becker MD primarily affect males, as the defective gene is on the X chromosome. Females can be carriers and may have mild symptoms.

Autosomal Dominant

Myotonic and facioscapulohumeral MD can be inherited from one affected parent, affecting both males and females equally.

Autosomal Recessive

Many limb-girdle types require mutations from both parents, with carriers typically showing no symptoms.

Risk Factors

The primary risk factor for muscular dystrophy is having a family history of the condition. However, spontaneous mutations can occur, meaning the disease can affect individuals with no family history.

Genetic Risk Factors

  • Family history of muscular dystrophy
  • Being a carrier of a muscular dystrophy gene mutation
  • Male gender (for X-linked types like Duchenne and Becker)
  • Consanguineous marriages (increases risk for recessive types)
  • Advanced paternal age (slightly increased risk of new mutations)

Factors Affecting Severity

  • Specific type of genetic mutation
  • Amount of functional protein produced
  • Age at symptom onset
  • Access to early intervention and treatment
  • Presence of genetic modifiers

Diagnosis

Diagnosing muscular dystrophy involves a combination of clinical evaluation, family history, and specialized tests. Early diagnosis is crucial for optimal management and family planning decisions.

Diagnostic Tests

Blood Tests

  • Creatine kinase (CK): Elevated levels indicate muscle damage
  • Genetic testing: Identifies specific mutations causing MD
  • Carrier testing: For family members at risk

Muscle Tests

  • Electromyography (EMG): Measures electrical activity in muscles
  • Muscle biopsy: Examines muscle tissue for dystrophin and other proteins
  • Immunohistochemistry: Visualizes specific proteins in muscle tissue

Imaging Studies

  • MRI: Shows muscle damage and fatty replacement
  • Ultrasound: Evaluates muscle structure
  • CT scan: Assesses muscle bulk and quality

Prenatal Testing: For families with a history of muscular dystrophy, prenatal testing through chorionic villus sampling or amniocentesis can detect affected fetuses.

Treatment Options

While there is no cure for muscular dystrophy, various treatments can help manage symptoms, maintain function, and improve quality of life. Treatment plans are individualized based on the type of MD, disease stage, and specific symptoms.

Medical Management

Corticosteroids

Prednisone and deflazacort can slow muscle degeneration in Duchenne MD, prolonging ambulation by 2-3 years. Regular monitoring for side effects is essential.

Cardiac Medications

ACE inhibitors and beta-blockers help manage cardiomyopathy, a common complication in many types of MD. Regular cardiac monitoring is crucial.

Gene-Targeted Therapies

  • Exon skipping drugs: Eteplirsen for specific DMD mutations
  • Stop codon read-through: Ataluren for nonsense mutations
  • Gene therapy: Emerging treatments delivering functional genes

Supportive Care

Physical Therapy

  • Range of motion exercises
  • Stretching to prevent contractures
  • Low-impact strengthening
  • Aquatic therapy

Respiratory Support

  • Breathing exercises
  • Cough assist devices
  • Non-invasive ventilation
  • Airway clearance techniques

Orthopedic Management

  • Braces and splints
  • Mobility aids (walkers, wheelchairs)
  • Spinal surgery for scoliosis
  • Tendon release surgeries

Lifestyle Modifications

  • Maintaining a healthy weight to reduce strain on weakened muscles
  • Nutritional support with adequate protein and vitamin D
  • Home modifications for accessibility
  • Psychological support and counseling
  • Educational accommodations for children

Prevention

As muscular dystrophy is a genetic condition, primary prevention is not possible. However, genetic counseling and testing can help families understand their risks and make informed decisions.

Genetic Counseling

Families with a history of muscular dystrophy should seek genetic counseling to:

  • Understand inheritance patterns and recurrence risks
  • Discuss carrier testing options
  • Learn about prenatal and preimplantation genetic testing
  • Make informed family planning decisions

Secondary Prevention

For those diagnosed with muscular dystrophy, preventing complications is crucial:

  • Regular cardiac monitoring to detect early heart involvement
  • Pulmonary function testing to monitor respiratory status
  • Bone density screening to prevent osteoporosis
  • Immunizations to prevent respiratory infections
  • Physical therapy to maintain function and prevent contractures

When to See a Doctor

Early recognition and diagnosis of muscular dystrophy can significantly improve outcomes through timely intervention. Parents should be alert to developmental concerns in children.

Seek Medical Evaluation For:

  • Delayed motor milestones (sitting, walking) in children
  • Frequent falls or clumsiness beyond typical age
  • Difficulty climbing stairs or rising from the floor
  • Walking on toes or with a waddling gait
  • Enlarged calf muscles in young children
  • Progressive muscle weakness at any age
  • Family history of muscular dystrophy

Emergency Symptoms

Seek immediate medical attention for:

  • Severe breathing difficulties or respiratory distress
  • Signs of heart failure (chest pain, severe fatigue, swelling)
  • Inability to swallow or risk of aspiration
  • Severe infections, especially respiratory

Frequently Asked Questions

Is muscular dystrophy always inherited?

While most cases are inherited, about one-third of Duchenne MD cases result from new mutations with no family history. Genetic testing can determine if a case is inherited or spontaneous.

Can females get muscular dystrophy?

Yes, females can be affected, though X-linked types like Duchenne primarily affect males. Females can be carriers and may have mild symptoms, while autosomal types affect both genders equally.

What is the life expectancy with muscular dystrophy?

Life expectancy varies greatly by type. With modern care, many with Duchenne MD live into their 30s or beyond, while those with milder forms may have normal lifespans.

Are there any promising new treatments?

Yes, gene therapy, exon skipping drugs, and CRISPR gene editing show promise. Several treatments have recently been approved, with many more in clinical trials.

References

  1. Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy. Lancet Neurol. 2018;17(3):251-267.
  2. Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies. Lancet. 2019;394(10213):2025-2038.
  3. Hoffman EP. The discovery of dystrophin, the protein product of the Duchenne muscular dystrophy gene. FEBS J. 2020;287(18):3870-3878.
  4. National Institute of Neurological Disorders and Stroke. Muscular Dystrophy Information Page. Updated 2023.
  5. Muscular Dystrophy Association. Types of Muscular Dystrophy and Neuromuscular Diseases. 2023.