Management of Limb-Girdle Muscular Dystrophy
Limb-girdle muscular dystrophy (LGMD) requires a multidisciplinary care approach with no FDA-approved disease-modifying therapies currently available, though gene replacement therapies are in clinical trials for recessive subtypes. 1, 2
Management Options
Neuromuscular and Functional Management
- Assess muscle strength and function every 6 months using manual muscle testing (MRC scale) and quantitative myometry, combined with standardized timed function tests (10-meter walk, Gowers' maneuver, 4-stair climb, rise from chair, 6-minute walk test). 3, 4
- Perform range of motion assessments using goniometry every 6 months to identify emerging muscle hypoextensibility and joint contractures that contribute to functional deterioration. 3
- Implement supervised aerobic exercise training as it has been shown safe and effective in improving oxidative capacity and muscle function in LGMD subtypes (LGMD2I, LGMD2L, LGMD2A), but avoid intense eccentric training due to risk of sarcolemma damage. 5
- Prescribe ankle-foot orthoses when ankle dorsiflexion weakness develops to prolong ambulation. 4
Cardiac Management
- Obtain baseline echocardiogram at diagnosis or by age 6 years, then repeat at maximum 24-month intervals until age 10, and annually thereafter, as certain LGMD mutations are associated with cardiac involvement. 4, 1, 6
- Initiate ACE inhibitors and beta-blockers at the first sign of cardiac dysfunction, even if asymptomatic. 3, 4
- Perform ECG and Holter monitoring regularly to detect arrhythmias and conduction abnormalities. 3, 7
Respiratory Management
- Perform pulmonary function testing every 6 months in non-ambulatory patients and every 6-12 months in ambulatory patients, measuring forced vital capacity (FVC), maximum inspiratory/expiratory pressure (MIP/MEP), and peak cough flow (PCF). 3, 4
- Monitor for symptoms of sleep-disordered breathing at every visit, as respiratory failure is the leading cause of mortality in neuromuscular disease. 3, 4
- Initiate noninvasive ventilation (NIV) when FVC declines, MIP/MEP is reduced, overnight oximetry is abnormal, or polysomnography shows sleep-disordered breathing. 4
- Ensure all patients receive scheduled vaccinations as per national guidelines to prevent respiratory infections. 3
Rehabilitation Services
- Provide physical and occupational therapy assessments every 4 months to implement aids, adaptations, and environmental controls as needed. 7
- Encourage appropriate exercise and activity to maintain muscle extensibility and minimize contractures, while supporting function and participation. 3
- Provide adaptive devices as appropriate for activities of daily living (self-care skills, writing, computer use, wheelchair control). 3
Orthopedic Management
- Consider surgical intervention (iliotibial band lengthening or Achilles tendon release) when contractures limit function or for foot positioning in wheelchair users. 3, 4
Psychosocial and Cognitive Support
- Perform comprehensive neuropsychological assessment at diagnosis to establish baseline cognitive function. 4, 7
- Screen regularly for depression, anxiety, obsessive-compulsive disorder, and attention-deficit hyperactivity disorder, with consideration of selective serotonin reuptake inhibitors for moderate to severe symptoms. 4
- Designate a care coordinator to serve as the family's point of contact and facilitate communication between clinicians. 4, 7
Nutritional Management
- Monitor weight at every visit using wheelchair-accessible scales, and perform nutritional assessment for over/underweight status. 3, 4
- Assess for dysphagia as the disease progresses, particularly in patients with bulbar involvement. 3
Genetic Counseling
- Offer genetic counseling and testing to all family members at risk, particularly female relatives who may be carriers in recessive forms. 8, 4
- Discuss family planning and prenatal diagnosis options with families. 8
Emerging Therapies
- Consider enrollment in clinical trials for gene replacement therapies, which are being tested for sarcoglycan and FKRP mutations in recessive LGMDs. 1, 2
- RNA-based therapeutic approaches may be amenable for dominant LGMDs. 1
Top 5 Complications to Monitor
1. Respiratory Failure
- Respiratory failure is the leading cause of mortality in neuromuscular disease and becomes more likely as upper limb weakness progresses (Brooke score ≥3). 3, 4
- Monitor for insidious symptoms including recurrent chest infections, inability to clear secretions, and sleep-disordered breathing. 3
2. Cardiomyopathy and Cardiac Dysfunction
- Certain LGMD mutations are associated with cardiac involvement, requiring early intervention even if asymptomatic. 1, 6
- Severe cardiomyopathy can impact respiratory function and overall prognosis. 3
3. Progressive Loss of Ambulation
- All LGMDs cause progressive disability and potential loss of ability to walk due to progressive muscle wasting. 1
- Loss of ambulation strongly correlates with progression of respiratory weakness. 3
4. Joint Contractures and Scoliosis
- Emerging muscle hypoextensibility and joint contractures contribute to functional deterioration and musculoskeletal problems. 3
- Significant scoliosis can impact respiratory function and complicate clinical assessment. 3, 4
5. Psychosocial and Cognitive Impairment
- Progressive disability leads to loss of ability to maintain employment and participate in daily activities. 1
- Depression, anxiety, and cognitive issues require regular screening and intervention. 4
Top 5 Parameters to Monitor
1. Pulmonary Function Tests
- Measure FVC, MIP/MEP (or SNIP), and PCF every 6 months in non-ambulatory patients and every 6-12 months in ambulatory patients. 3, 4
- Record patient position during testing to allow better comparison of serial measurements. 3
2. Cardiac Function
- Perform echocardiogram at baseline, then at maximum 24-month intervals until age 10, and annually thereafter. 4
- Obtain ECG and Holter monitoring regularly to detect arrhythmias and conduction abnormalities. 3, 7
3. Muscle Strength and Function
- Assess using manual muscle testing and quantitative myometry every 6 months during the ambulatory phase. 3, 4
- Perform standardized timed function tests (10-meter walk, Gowers' maneuver, 4-stair climb, rise from chair, 6-minute walk test) every 6 months. 3, 4
4. Range of Motion and Contractures
- Use goniometry to assess hip, knee, ankle joints, iliotibial band, hamstrings, and gastrocnemius in lower extremities, and elbow, wrist, and long finger flexors in upper extremities. 3
- Identify need for additional therapeutic or surgical intervention (orthoses, splinting, standers, iliotibial band lengthening). 3