What are the management and treatment options for an adult patient with a family history of muscular dystrophy and a confirmed contraction of the D4Z4 repeat array on chromosome 4q35, associated with the DUX4 gene, indicative of facioscapulohumeral muscular dystrophy (FSHD)?

Management of Facioscapulohumeral Muscular Dystrophy (FSHD)

There is no disease-modifying pharmacological treatment currently available for FSHD, so management focuses on multidisciplinary supportive care including physical therapy to prevent contractures, occupational therapy for functional adaptations, and cardiac/respiratory monitoring to detect and manage complications early.

Understanding the Genetic Diagnosis

The confirmed contraction of the D4Z4 repeat array on chromosome 4q35 with DUX4 gene involvement establishes the diagnosis of FSHD type 1 (FSHD1), which accounts for approximately 95% of FSHD cases 1. This genetic abnormality leads to inappropriate expression of the DUX4 protein in skeletal muscle, causing muscle cell toxicity and progressive degeneration 1, 2. The DUX4 protein induces apoptosis, inhibits myogenesis, and sensitizes cells to oxidative stress 2, 3.

Important caveat: DUX4 expression alone does not guarantee disease manifestation or severity, as quantitative modifiers and family genetic background influence disease progression 4. Some genetically affected individuals may remain asymptomatic or minimally symptomatic for years 4.

Clinical Monitoring Schedule

Establish a structured surveillance program with the following frequency:

• Neuromuscular assessments every 6 months to monitor disease progression, similar to the monitoring approach used in other muscular dystrophies 5, 6
• Physical and occupational therapy evaluations every 4 months to assess functional status and adjust interventions 5
• Annual cardiac evaluation with ECG and echocardiogram starting at diagnosis, as cardiomyopathy can develop in muscular dystrophies 6
• Annual pulmonary function testing once respiratory symptoms emerge or functional decline accelerates 5

Physical and Occupational Therapy Interventions

The cornerstone of FSHD management is preventing secondary complications through targeted therapy:

• Range of motion assessments focusing on hip, knee, ankle joints, iliotibial band, hamstrings, and gastrocnemius in lower extremities; elbow, wrist, and long finger flexors in upper extremities 5
• Gentle stretching and low-resistance exercise to maintain muscle function without causing overwork damage 5
• Orthotic devices and splinting when contractures begin developing to preserve function 5
• Assistive devices including manual or electric wheelchairs, environmental controls, and adaptive equipment for activities of daily living as disease progresses 5

Critical pitfall to avoid: Aggressive strengthening exercises can accelerate muscle damage in FSHD; therapy should emphasize gentle activity and contracture prevention rather than intensive strengthening 5.

Functional Assessment Tools

Monitor disease progression using standardized measures:

• Timed functional tests: 10-meter walk, Gowers' maneuver, climbing 4 stairs, rising from chair, 6-minute walk test during ambulatory phase 5
• Upper extremity function: Time to put on a shirt, self-care skills, writing, computer use as disease advances 5
• Validated scales: Vignos lower extremity scale, Brooke upper extremity scale, or motor function measures to track progression objectively 5

Pharmacological Considerations

Unlike Duchenne muscular dystrophy, glucocorticoids have not been proven effective in FSHD and are not recommended 5. The pathophysiology differs fundamentally—FSHD results from toxic gain-of-function of DUX4 protein rather than dystrophin deficiency 1, 3.

No FDA-approved disease-modifying therapies currently exist for FSHD. Clinical trials are investigating potential treatments targeting DUX4 expression, but these remain experimental.

Cardiac and Respiratory Management

Proactive monitoring prevents life-threatening complications:

• Baseline and annual cardiac evaluation to detect cardiomyopathy or conduction abnormalities, which can occur in muscular dystrophies 5, 6
• Pulmonary function testing when forced vital capacity declines or respiratory symptoms develop 5
• Consider non-invasive ventilation if nocturnal hypoventilation or respiratory insufficiency develops 5

Genetic Counseling and Family Screening

All first-degree relatives require genetic counseling and consideration for testing:

• Female relatives should receive carrier testing, as FSHD shows autosomal dominant inheritance with variable penetrance 6, 7
• Family planning discussions should include prenatal diagnosis options 8
• Asymptomatic carriers may benefit from early monitoring even without clinical manifestations 4

Psychosocial Support

Provide continuous education and realistic expectations about disease course:

• Connect patients with FSHD patient organizations for peer support and resources 8
• Address psychological impact of progressive disability and functional losses 5
• Discuss workplace accommodations and disability planning as disease advances 5

Emerging Therapies

While no approved treatments exist, patients should be informed about ongoing clinical trials investigating DUX4-targeted therapies, as the understanding of FSHD pathogenesis through DUX4 expression has opened potential therapeutic avenues 1, 3.