What is the recommended management plan for a patient with a positive DMD (Duchenne Muscular Dystrophy) gene?

Management of DMD Gene-Positive Patients

Initiate daily glucocorticoid therapy with prednisone 0.75 mg/kg/day (or deflazacort 0.9 mg/kg/day if weight/behavioral concerns exist) during the plateau phase of motor function, typically between ages 4-8 years, when motor skills stop progressing but before clear decline begins. 1

Timing of Glucocorticoid Initiation

Do not start glucocorticoids in children under 2 years who are still gaining motor skills. 1 The typical DMD patient continues making motor progress until approximately 4-6 years of age, albeit slower than peers 2.

Three Phases to Guide Treatment Timing:

• Making progress phase: Child continues gaining motor skills; glucocorticoids not recommended 2
• Plateau phase (age 4-8 years): No longer progressing in motor skills but not yet declining; this is the optimal time to initiate therapy 2, 1
• Decline phase: Child takes longer in timed testing, loses skills (e.g., climbing stairs), shows less endurance, or has more falls; starting steroids is still recommended but may offer more limited benefit 2

Complete all recommended immunizations and establish varicella immunity before starting glucocorticoids. 2, 1

Glucocorticoid Selection and Dosing

First-Line Options:

• Prednisone 0.75 mg/kg/day (maximum 40 mg/day): First-line choice unless pre-existing weight or behavioral issues exist 1, 3
• Deflazacort 0.9 mg/kg/day: Consider as first-line when pre-existing weight or behavioral concerns are present 1

Evidence shows 0.75 mg/kg/day prednisone is superior to 0.3 mg/kg/day on most strength and function measures, with little additional benefit at 1.5 mg/kg/day. 4

Managing Side Effects:

• If side effects are unmanageable/intolerable, reduce dose by 25-33% and reassess in 1 month 2
• If obesity is concerning, switch from prednisone to deflazacort 2
• Do not abandon glucocorticoid therapy until at least one dose reduction and change to alternative regimen has been attempted 2, 1
• Provide families with a steroid card listing emergency considerations for acute illness, fracture, infection, or surgery 2, 1

Cardiac Management

Initiate ACE inhibitors or ARBs by 10 years of age (barring contraindications). 1 This is critical as cardiomyopathy is a major cause of morbidity and mortality in DMD.

Consider β-adrenergic blockade after ACE inhibitor/ARB initiation, especially with ventricular dysfunction or elevated heart rate. 1

Respiratory Management

• Regular pulmonary function monitoring is essential 1
• Assess for sleep hypoventilation with sleep studies or nocturnal oximetry 1
• Preoperative pulmonologist evaluation at least 2 months before any surgery 1
• Glucocorticoids stabilize pulmonary function and delay need for noninvasive ventilation 1

Orthopedic Management

Consider surgical intervention for scoliosis when Cobb angle reaches 30-50 degrees. 1 Glucocorticoid therapy reduces risk of progressive scoliosis and need for spinal surgery 1.

No absolute pulmonary function contraindications exist for surgery; patients with FVC as low as 20% of predicted have had good outcomes. 1

Multidisciplinary Monitoring Schedule

• Physical and occupational therapy assessments every 4 months 1
• Routine clinic appointments every 6 months 1
• Emotional adjustment screening at every clinic visit (can be informal; use short standardized rating scales) 2, 1
• Comprehensive developmental assessment (≤4 years) or neuropsychological assessment (≥5 years) at or near time of diagnosis and prior to entering formal schooling 2, 1

Neurocognitive and Psychosocial Support

Screen emotional status at every clinic visit using standardized rating scales; can be completed by social worker, mental health professional, or trained clinical staff. 2

Comprehensive neuropsychological assessment should use standardized performance-based tests and parent/patient rating scales, conducted by a neuropsychologist or professional with expertise in brain functioning within medical conditions. 2

Assess younger children with suspected speech/language delays for therapy services. 2

Supplements and Alternative Therapies

Do not use supplements including coenzyme Q10, carnitine, amino acids, fish oil, vitamin E, or green tea extract—insufficient evidence exists for recommendation. 2, 1 If a patient is taking creatine and develops renal dysfunction, discontinue immediately 2.

Oxandrolone (anabolic steroid) is not appropriate either with or without glucocorticoid therapy. 2

Botulinum toxin A has not been studied for safety in DMD and is inappropriate for contracture treatment/prevention. 2

Common Pitfalls to Avoid

• Starting glucocorticoids too early (before plateau phase in children under 4 years still gaining skills) can expose patients to unnecessary side effects without clear benefit 2
• Abandoning glucocorticoids prematurely due to side effects without attempting dose reduction or alternative regimens deprives patients of proven mortality and morbidity benefits 2, 1
• Failing to provide steroid emergency card puts patients at risk during acute illness or surgical procedures 2, 1
• Delaying cardiac prophylaxis beyond age 10 misses the window for preventing cardiomyopathy progression 1