Facioscapulohumeral Muscular Dystrophy in Children

Introduction to Facioscapulohumeral Muscular Dystrophy (FSHD)

Facioscapulohumeral Muscular Dystrophy (FSHD) is one of the most common forms of muscular dystrophy, characterized by progressive weakness of the facial, shoulder girdle, and upper arm muscles, with variable involvement of lower extremities.

  • Incidence: Approximately 1 in 8,000 to 22,000 individuals
  • Inheritance: Autosomal dominant (95% FSHD1, 5% FSHD2)
  • Onset: Can occur from infancy to adulthood, but typically in teens to early 20s
  • Progression: Usually slow, with periods of rapid deterioration
  • Life expectancy: Generally normal, but severe cases may have reduced lifespan

Pathophysiology of FSHD

FSHD has a unique genetic mechanism compared to other muscular dystrophies:

  1. FSHD1 (95% of cases):
    • Contraction of D4Z4 macrosatellite repeat array on chromosome 4q35
    • Normal individuals have 11-100 repeats; FSHD1 patients have 1-10 repeats
    • Leads to chromatin relaxation and expression of DUX4 gene
  2. FSHD2 (5% of cases):
    • Mutations in SMCHD1 or DNMT3B genes
    • Results in similar chromatin relaxation and DUX4 expression
  3. DUX4 toxicity:
    • Inappropriate expression of DUX4 in skeletal muscle
    • Activates germline genes and retrotransposons
    • Induces apoptosis and interferes with myogenesis
  4. Muscle fiber degeneration:
    • Inflammatory changes and fatty infiltration
    • Preferential involvement of certain muscle groups
  5. Epigenetic factors:
    • Influence disease severity and progression
    • Explain variability in clinical presentation

Clinical Presentation of FSHD in Children

FSHD in children can present with varying severity and progression:

  • Early-onset FSHD (before age 10):
    • Facial weakness: Incomplete eye closure, inability to purse lips
    • Shoulder girdle weakness: Scapular winging, difficulty raising arms
    • Abdominal muscle weakness: Protuberant abdomen
    • Foot dorsiflexor weakness: Foot drop, frequent tripping
  • Infantile FSHD (rare, severe form):
    • Facial diplegia in infancy
    • Global developmental delay
    • Early respiratory insufficiency
    • Epilepsy and cognitive impairment in some cases
  • Classic presentation (often in teens):
    • Asymmetric facial weakness
    • Scapular winging and difficulty raising arms above shoulder level
    • Steppage gait due to foot dorsiflexor weakness
  • Associated features:
    • High-frequency hearing loss (up to 75% of cases)
    • Retinal telangiectasias (up to 60% of cases)
    • Rarely, cardiac arrhythmias

Note: There is significant variability in disease severity, even within families.

Diagnosis of FSHD

Diagnosis of FSHD involves clinical assessment, genetic testing, and supportive investigations:

  1. Clinical evaluation:
    • Characteristic pattern of muscle weakness
    • Family history (although 10-30% are de novo mutations)
  2. Genetic testing:
    • For FSHD1: Southern blot or molecular combing to detect D4Z4 contractions
    • For FSHD2: Sequencing of SMCHD1 or DNMT3B genes
  3. Serum creatine kinase (CK):
    • Normal to mildly elevated (typically less than 5 times upper limit of normal)
  4. Muscle imaging:
    • MRI or CT to assess pattern of muscle involvement
    • Characteristic sparing of certain muscles (e.g., deltoids, psoas)
  5. Muscle biopsy:
    • Not routinely required for diagnosis
    • If performed, shows non-specific dystrophic changes
  6. Electromyography (EMG):
    • May show myopathic changes
    • Not necessary for diagnosis
  7. Audiometry:
    • To assess for high-frequency hearing loss
  8. Ophthalmological examination:
    • To evaluate for retinal vascular abnormalities

Management of FSHD in Children

Management of FSHD is primarily supportive and focuses on maintaining function and quality of life:

  1. Physical therapy and rehabilitation:
    • Stretching exercises to maintain flexibility
    • Low to moderate intensity aerobic exercise
    • Avoid excessive resistance training
  2. Occupational therapy:
    • Adaptive devices to maintain independence
    • Strategies for energy conservation
  3. Orthotic interventions:
    • Ankle-foot orthoses for foot drop
    • Scapular fixation devices in select cases
  4. Pain management:
    • Address chronic pain associated with muscle weakness
    • May include physical modalities, medications, or complementary therapies
  5. Respiratory care:
    • Monitor pulmonary function, especially in severe cases
    • Non-invasive ventilation if needed
  6. Cardiac monitoring:
    • Periodic ECG and echocardiogram
    • Management of arrhythmias if present
  7. Ophthalmological care:
    • Management of incomplete eye closure (e.g., artificial tears, eyelid surgery)
    • Monitoring of retinal vascular changes
  8. Audiology:
    • Regular hearing assessments
    • Hearing aids if necessary
  9. Nutritional support:
    • Maintain healthy weight to optimize mobility
    • Address swallowing difficulties if present
  10. Psychosocial support:
    • Counseling for patients and families
    • School accommodations as needed
  11. Emerging therapies:
    • Clinical trials targeting DUX4 expression or its downstream effects
    • Potential for antisense oligonucleotides or small molecule therapies

Prognosis of FSHD in Children

The prognosis for children with FSHD is variable and depends on several factors:

  • Disease progression:
    • Usually slow, but can have periods of rapid deterioration
    • About 20% of patients become wheelchair-dependent by age 50
  • Age of onset:
    • Earlier onset generally associated with more severe disease
    • Infantile FSHD has a poorer prognosis
  • Genetic factors:
    • Smaller D4Z4 repeat sizes correlate with more severe disease
    • Presence of certain modifier genes may influence severity
  • Respiratory function:
    • Less than 1% of patients require ventilatory support
    • More common in early-onset or severe cases
  • Life expectancy:
    • Generally normal in most cases
    • May be reduced in severe, early-onset forms
  • Quality of life:
    • Can be significantly impacted by physical limitations
    • Psychosocial support and adaptations can improve outcomes

Note: The clinical course can be highly variable, even within families with the same genetic mutation.



Facioscapulohumeral Muscular Dystrophy in Children
  1. What is the genetic cause of Facioscapulohumeral Muscular Dystrophy (FSHD)?
    FSHD is caused by a deletion of DNA repeats in the D4Z4 region of chromosome 4q35.
  2. Which muscle groups are typically affected first in children with FSHD?
    The facial muscles (facio-), shoulder girdle (scapulo-), and upper arms (humeral) are usually affected first.
  3. What is the typical age of onset for FSHD in children?
    FSHD typically manifests in late childhood to early adulthood, but infantile cases can occur.
  4. How is FSHD inherited?
    FSHD is inherited in an autosomal dominant pattern.
  5. What percentage of FSHD cases are due to de novo mutations?
    Approximately 10-30% of FSHD cases are due to de novo mutations.
  6. What is the diagnostic gold standard for FSHD?
    The diagnostic gold standard for FSHD is genetic testing to detect D4Z4 repeat contractions.
  7. Which non-muscular symptoms can be associated with FSHD in children?
    Non-muscular symptoms can include high-frequency hearing loss and retinal vascular abnormalities.
  8. What is the typical pattern of muscle weakness progression in FSHD?
    Weakness typically progresses in a descending pattern, from face and shoulders to upper arms, trunk, and legs.
  9. How does FSHD affect a child's ability to smile?
    FSHD can cause facial weakness, resulting in difficulty smiling or closing eyes fully (sleeping with eyes partially open).
  10. What percentage of children with FSHD eventually require a wheelchair?
    Approximately 20% of individuals with FSHD eventually require a wheelchair, typically in adulthood.
  11. How does FSHD impact respiratory function in children?
    Severe cases of FSHD can lead to respiratory insufficiency, but it's less common in children compared to adults.
  12. What is the role of physical therapy in managing FSHD in children?
    Physical therapy helps maintain muscle strength, prevent contractures, and improve overall function and mobility.
  13. How does FSHD affect a child's ability to raise their arms above their head?
    FSHD often causes significant weakness in the shoulder muscles, making it difficult to raise arms above shoulder level.
  14. What is the typical life expectancy for children diagnosed with FSHD?
    Life expectancy is generally normal, though severe cases may have slightly reduced life expectancy due to complications.
  15. How does FSHD differ between Type 1 and Type 2?
    Type 1 FSHD is caused by D4Z4 repeat contraction, while Type 2 is clinically similar but caused by SMCHD1 gene mutations.
  16. What percentage of children with FSHD experience pain as a symptom?
    Approximately 50-80% of individuals with FSHD report pain, often in the lower back, shoulders, and legs.
  17. How does FSHD affect a child's ability to participate in sports?
    FSHD can limit participation in some sports due to muscle weakness, but low-impact activities are often encouraged.
  18. What is the risk of cardiac involvement in children with FSHD?
    Cardiac involvement is rare in FSHD, occurring in less than 5% of cases, usually as arrhythmias.
  19. How does FSHD impact a child's speech and swallowing abilities?
    Severe facial weakness can affect speech clarity and, in rare cases, cause swallowing difficulties.
  20. What is the role of genetic counseling for families with a child diagnosed with FSHD?
    Genetic counseling provides information about inheritance patterns, recurrence risks, and family planning options.
  21. How does FSHD progression differ between children and adults?
    FSHD progression is typically slower in children compared to adult-onset cases, but early-onset can indicate more severe disease.
  22. What is the significance of the "scapular winging" sign in children with FSHD?
    "Scapular winging" is a characteristic sign of FSHD, caused by weakness of the muscles that stabilize the shoulder blade.
  23. How does FSHD affect a child's posture and gait?
    FSHD can cause lordosis (increased lower back curvature) and a waddling gait due to hip girdle weakness.
  24. What is the role of occupational therapy in managing FSHD in children?
    Occupational therapy helps children adapt to muscle weakness, improve daily living skills, and maintain independence.
  25. How does FSHD impact a child's cognitive development?
    FSHD does not typically affect cognitive function; intellectual development is usually normal.
  26. What is the current status of gene therapy research for FSHD in children?
    Gene therapy research is ongoing, focusing on suppressing DUX4 gene expression, but is still in preclinical stages.
  27. How does FSHD affect growth and puberty in children?
    FSHD does not typically affect growth or puberty; these processes usually progress normally.
  28. What is the role of corticosteroids in treating FSHD in children?
    Unlike some other muscular dystrophies, corticosteroids are not routinely used to treat FSHD.
  29. How does FSHD impact sleep quality in children?
    FSHD can affect sleep due to breathing difficulties, inability to adjust position, or discomfort from muscle weakness.
  30. What is the importance of regular ophthalmological check-ups for children with FSHD?
    Regular eye exams are important to monitor for retinal vascular abnormalities, which occur in about 60% of FSHD patients.


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