Duchenne & Becker Muscular Dystrophies in Children

Introduction to Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy (DMD) is the most common and severe form of childhood muscular dystrophy. It is an X-linked recessive disorder caused by mutations in the dystrophin gene, resulting in progressive muscle weakness and degeneration.

  • Incidence: Approximately 1 in 3,500 to 5,000 male births
  • Onset: Usually between 2 and 5 years of age
  • Progression: Rapid, with loss of ambulation typically by early teens
  • Life expectancy: Late 20s to early 30s (with current management strategies)

Pathophysiology of DMD

The pathophysiology of DMD centers around the absence or dysfunction of dystrophin, a crucial protein for muscle fiber integrity.

  1. Genetic basis: Mutations in the DMD gene on the X chromosome (Xp21)
  2. Dystrophin deficiency: Results in instability of the sarcolemma during muscle contraction
  3. Muscle fiber damage: Leads to repeated cycles of necrosis and regeneration
  4. Fibrosis and fatty infiltration: Progressive replacement of muscle tissue
  5. Systemic effects: Cardiac involvement, respiratory compromise, and potential cognitive impairment

Clinical Presentation of DMD

The clinical features of DMD typically progress in a predictable pattern:

  • Early signs (2-5 years):
    • Delayed motor milestones
    • Difficulty rising from the floor (Gowers' sign)
    • Waddling gait
    • Frequent falls
  • Progressive weakness (5-12 years):
    • Proximal muscle weakness, especially in lower limbs
    • Pseudohypertrophy of calf muscles
    • Loss of ability to run and climb stairs
  • Loss of ambulation (by early teens):
    • Wheelchair dependence
    • Development of scoliosis
  • Late-stage complications:
    • Respiratory insufficiency
    • Cardiomyopathy
    • Swallowing difficulties

Note: Cognitive impairment may be present in some cases, typically manifesting as learning difficulties or behavioral issues.

Diagnosis of DMD

Diagnosis of DMD involves a combination of clinical assessment, laboratory tests, and genetic analysis:

  1. Clinical suspicion: Based on characteristic presenting features
  2. Serum creatine kinase (CK): Markedly elevated (often >10,000 IU/L)
  3. Genetic testing:
    • Multiplex ligation-dependent probe amplification (MLPA)
    • Next-generation sequencing (NGS)
    • Identifies specific mutation in the DMD gene
  4. Muscle biopsy: If genetic testing is inconclusive
    • Absence of dystrophin on immunohistochemistry
    • Characteristic dystrophic changes on histology
  5. Electromyography (EMG): May show myopathic changes
  6. Carrier testing: Genetic counseling and testing for female relatives

Management of DMD

Management of DMD requires a multidisciplinary approach focusing on supportive care and emerging therapies:

  1. Corticosteroids:
    • Prednisone or deflazacort
    • Slows disease progression and preserves muscle function
    • Careful monitoring for side effects
  2. Physical therapy and rehabilitation:
    • Regular stretching to prevent contractures
    • Assistive devices for mobility
    • Orthotic interventions
  3. Respiratory management:
    • Regular pulmonary function tests
    • Non-invasive ventilation as needed
    • Chest physiotherapy and cough assistance
  4. Cardiac care:
    • Regular echocardiograms and ECGs
    • ACE inhibitors and beta-blockers for cardiomyopathy
  5. Orthopedic interventions:
    • Surgical management of scoliosis if needed
    • Tendon release procedures for contractures
  6. Nutritional support:
    • Maintaining healthy weight
    • Gastrostomy tube placement if swallowing difficulties develop
  7. Emerging therapies:
    • Exon skipping (e.g., eteplirsen for exon 51 skippable mutations)
    • Ataluren for nonsense mutations
    • Gene therapy approaches in clinical trials
  8. Psychosocial support:
    • Educational accommodations
    • Family counseling
    • Addressing mental health concerns

Prognosis of DMD

The prognosis for individuals with DMD has improved significantly with advancements in care:

  • Life expectancy: Now extended into late 20s to early 30s
  • Ambulatory phase: Typically maintained until early teens with corticosteroid therapy
  • Respiratory function: Decline can be slowed with proactive management
  • Cardiac complications: Remain a significant cause of morbidity and mortality
  • Quality of life: Improved with multidisciplinary care and assistive technologies

Factors influencing prognosis:

  • Age at diagnosis and initiation of treatment
  • Specific genetic mutation and its effect on dystrophin production
  • Adherence to treatment regimens
  • Access to comprehensive care
  • Development of novel therapies

Introduction to Becker Muscular Dystrophy (BMD)

Becker Muscular Dystrophy (BMD) is a milder form of dystrophinopathy, related to but less severe than Duchenne Muscular Dystrophy (DMD). It is an X-linked recessive disorder caused by mutations in the dystrophin gene that result in partially functional dystrophin protein.

  • Incidence: Approximately 1 in 18,000 to 31,000 male births
  • Onset: Usually between 5 and 15 years of age, but can occur later
  • Progression: Slower than DMD, with variable severity
  • Life expectancy: Often into 40s or 50s, some may have normal lifespan

Pathophysiology of BMD

The pathophysiology of BMD is similar to DMD but less severe due to the presence of partially functional dystrophin:

  1. Genetic basis: Mutations in the DMD gene on the X chromosome (Xp21)
  2. Dystrophin production: Reduced amount or altered structure of dystrophin protein
  3. Muscle fiber instability: Less severe than in DMD, but still present
  4. Muscle degeneration: Slower progression of muscle weakness and fibrosis
  5. Systemic effects: Potential cardiac involvement, milder respiratory issues

Key difference from DMD: In BMD, the genetic mutation allows for the production of some functional dystrophin, leading to a milder phenotype.

Clinical Presentation of BMD

The clinical features of BMD are similar to DMD but generally milder and with later onset:

  • Early signs (often 5-15 years, but can be later):
    • Mild delay in motor milestones (less common than in DMD)
    • Difficulty running or climbing stairs
    • Muscle cramps with exercise
  • Progressive weakness (variable rate):
    • Proximal muscle weakness, especially in lower limbs
    • Calf hypertrophy (may be less pronounced than in DMD)
    • Preservation of ambulation into adulthood in many cases
  • Later-stage manifestations:
    • Gradual loss of ambulation (often in 3rd to 4th decade)
    • Development of contractures
    • Potential for scoliosis (less common than in DMD)
  • Cardiac involvement:
    • Can be a significant feature, sometimes preceding skeletal muscle weakness
    • Cardiomyopathy and arrhythmias may occur

Note: Cognitive function is typically normal in BMD, although mild cognitive issues can occur in some cases.

Diagnosis of BMD

Diagnosis of BMD involves clinical assessment, laboratory tests, and genetic analysis:

  1. Clinical suspicion: Based on presenting features and family history
  2. Serum creatine kinase (CK): Elevated, but often less than in DMD (typically 5-100 times normal)
  3. Genetic testing:
    • Multiplex ligation-dependent probe amplification (MLPA)
    • Next-generation sequencing (NGS)
    • Identifies specific mutation in the DMD gene
  4. Muscle biopsy: If genetic testing is inconclusive
    • Reduced or abnormal dystrophin on immunohistochemistry
    • Dystrophic changes on histology, often less severe than in DMD
  5. Western blot analysis: Can quantify dystrophin levels
  6. Electromyography (EMG): May show myopathic changes
  7. Cardiac evaluation: ECG and echocardiogram to assess cardiac involvement
  8. Carrier testing: Genetic counseling and testing for female relatives

Management of BMD

Management of BMD requires a multidisciplinary approach, tailored to the individual's needs:

  1. Physical therapy and rehabilitation:
    • Regular stretching to prevent contractures
    • Appropriate exercise regimens to maintain muscle strength
    • Assistive devices as needed for mobility
  2. Cardiac management:
    • Regular cardiac evaluations (ECG, echocardiogram)
    • Early initiation of cardioprotective medications (ACE inhibitors, beta-blockers)
    • Management of arrhythmias if present
  3. Respiratory care:
    • Pulmonary function tests as needed
    • Non-invasive ventilation if respiratory insufficiency develops
  4. Orthopedic interventions:
    • Management of contractures
    • Surgical intervention for severe contractures or scoliosis if needed
  5. Pain management:
    • Addressing muscle cramps and pain
    • Consider non-steroidal anti-inflammatory drugs or other pain medications
  6. Nutritional support:
    • Maintaining healthy weight to optimize mobility
    • Calcium and Vitamin D supplementation for bone health
  7. Corticosteroids:
    • Not routinely used in BMD as in DMD
    • May be considered in some cases to slow progression
  8. Emerging therapies:
    • Potential for exon skipping therapies in some mutations
    • Gene therapy approaches in clinical trials
  9. Psychosocial support:
    • Counseling and support for patients and families
    • Vocational training and support for adults with BMD

Prognosis of BMD

The prognosis for individuals with BMD is generally more favorable than for those with DMD:

  • Life expectancy: Often into 40s or 50s, some may have normal lifespan
  • Ambulation: Many maintain ability to walk into adulthood, some throughout life
  • Cardiac function: Major determinant of prognosis; early intervention can improve outcomes
  • Respiratory function: Usually less severely affected than in DMD
  • Quality of life: Can be good with appropriate management and support

Factors influencing prognosis:

  • Specific genetic mutation and its effect on dystrophin production
  • Age at onset of symptoms
  • Rate of disease progression
  • Presence and severity of cardiac involvement
  • Access to comprehensive care
  • Adherence to management recommendations


Duchenne & Becker Muscular Dystrophies in Children
  1. What is the genetic cause of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)?
    Both DMD and BMD are caused by mutations in the dystrophin gene on the X chromosome.
  2. How do Duchenne and Becker Muscular Dystrophies differ?
    DMD results in absence of functional dystrophin, while BMD produces partially functional dystrophin, leading to a milder phenotype.
  3. What is the typical age of onset for Duchenne Muscular Dystrophy?
    DMD typically presents between ages 2-5 with motor developmental delays and muscle weakness.
  4. How is Duchenne Muscular Dystrophy inherited?
    DMD is inherited in an X-linked recessive pattern, primarily affecting males.
  5. What are the early signs of Duchenne Muscular Dystrophy in children?
    Early signs include delayed walking, difficulty climbing stairs, frequent falls, and Gowers' sign when rising from the floor.
  6. How is Duchenne Muscular Dystrophy diagnosed?
    Diagnosis involves clinical presentation, elevated creatine kinase levels, genetic testing, and sometimes muscle biopsy.
  7. What is the Gowers' sign and why is it significant in DMD?
    Gowers' sign is when a child uses their hands to "climb" up their legs to stand, indicating proximal muscle weakness typical in DMD.
  8. How does Duchenne Muscular Dystrophy affect a child's cardiac function?
    DMD can lead to cardiomyopathy and heart failure, typically becoming evident in the teenage years.
  9. What is the role of corticosteroids in treating Duchenne Muscular Dystrophy?
    Corticosteroids can slow disease progression, preserve muscle strength and function, and delay the loss of ambulation.
  10. How does Duchenne Muscular Dystrophy affect a child's respiratory function?
    DMD progressively weakens respiratory muscles, leading to decreased lung function and eventual need for ventilatory support.
  11. What is the typical life expectancy for children with Duchenne Muscular Dystrophy?
    With current treatments, many individuals with DMD now live into their 30s or 40s.
  12. How does Duchenne Muscular Dystrophy affect a child's cognitive development?
    Some children with DMD may have mild cognitive impairment or learning difficulties, particularly in verbal skills.
  13. What is the importance of regular physiotherapy in managing DMD?
    Regular physiotherapy helps maintain muscle flexibility, prevent contractures, and optimize function.
  14. How does Duchenne Muscular Dystrophy affect a child's spine?
    DMD can lead to scoliosis, especially after loss of ambulation, which may require surgical intervention.
  15. What is the role of genetic counseling for families with a child diagnosed with DMD?
    Genetic counseling provides information about inheritance, recurrence risks, and options for future pregnancies.
  16. How does Duchenne Muscular Dystrophy affect a child's ability to walk?
    Most children with DMD lose the ability to walk between ages 10-14, requiring wheelchair use.
  17. What nutritional considerations are important for children with DMD?
    Balanced nutrition is crucial, with attention to preventing obesity while ensuring adequate calorie and protein intake.
  18. How does Duchenne Muscular Dystrophy affect a child's bone health?
    DMD and long-term corticosteroid use can lead to osteoporosis, increasing fracture risk.
  19. What is the role of assistive devices in managing DMD?
    Assistive devices like wheelchairs, orthotics, and adaptive equipment help maintain independence and quality of life.
  20. How does puberty affect the progression of Duchenne Muscular Dystrophy?
    The hormonal changes of puberty can accelerate muscle weakness and may affect the response to corticosteroid treatment.
  21. What is the current status of gene therapy research for DMD?
    Gene therapy approaches, including exon skipping and gene replacement, are in clinical trials with promising early results.
  22. How does Duchenne Muscular Dystrophy affect a child's social and emotional development?
    DMD can impact social interactions and emotional well-being, necessitating psychological support and adaptive strategies.
  23. What is the importance of multidisciplinary care in managing DMD?
    Multidisciplinary care involving neurologists, cardiologists, pulmonologists, and therapists is crucial for comprehensive management.
  24. How does Duchenne Muscular Dystrophy affect a child's sleep patterns?
    DMD can cause sleep disturbances due to breathing difficulties, positioning issues, and pain.
  25. What is the role of occupational therapy in managing DMD?
    Occupational therapy helps maintain independence in daily activities through adaptive techniques and equipment.
  26. How does Duchenne Muscular Dystrophy affect a child's gastrointestinal function?
    DMD can lead to issues like constipation, gastroesophageal reflux, and difficulties with chewing and swallowing.
  27. What is the importance of regular cardiac monitoring in children with DMD?
    Regular cardiac monitoring helps detect and manage cardiomyopathy, a common complication of DMD.
  28. How does Duchenne Muscular Dystrophy affect a child's ability to participate in school activities?
    DMD necessitates accommodations for physical limitations and potential learning difficulties in the school environment.
  29. What is the role of non-invasive ventilation in managing DMD?
    Non-invasive ventilation, typically starting with nighttime use, helps manage respiratory insufficiency as the disease progresses.
  30. How does Becker Muscular Dystrophy differ from DMD in terms of progression and management?
    BMD typically has a later onset, slower progression, and longer preservation of ambulation compared to DMD, but management principles are similar.


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