What is the diagnosis and treatment approach for muscular atrophy in children?

Muscular Atrophy in Children: Diagnosis and Treatment

Diagnostic Approach

The first step when evaluating a child with suspected muscular atrophy is to measure serum creatine kinase (CK) levels, followed by targeted genetic testing based on clinical presentation, before considering invasive procedures like muscle biopsy. 1

Initial Clinical Assessment

• Evaluate deep tendon reflexes carefully: Decreased or absent reflexes with hypotonia indicate lower motor neuron disease (such as spinal muscular atrophy), while preserved or increased reflexes suggest upper motor neuron dysfunction or myopathy 2
• Assess motor milestones: Delayed walking beyond 16-18 months, frequent falls, difficulty climbing stairs, or positive Gowers' sign are red flags requiring immediate evaluation 1
• Examine for calf pseudohypertrophy: This finding combined with proximal muscle weakness strongly suggests Duchenne muscular dystrophy 3
• Check eye movements: Normal eye fixation effectively rules out severe congenital myopathies, which typically present with ophthalmoplegia 2

Laboratory Testing Algorithm

CK Level Interpretation:

• CK >10,000 U/L: Highly suggestive of Duchenne muscular dystrophy and requires immediate dystrophin gene testing 3
• Normal CK: Essentially excludes muscular dystrophies and points toward neurogenic causes like spinal muscular atrophy 2
• Important caveat: In DMD, CK levels remain permanently elevated (typically >10,000 U/L) and do not fluctuate with exercise, unlike healthy individuals where exercise-induced elevations return to normal within 24-120 hours 3

Genetic Testing:

• For suspected DMD: Proceed directly to dystrophin gene deletion/duplication analysis from blood sample 3
• For suspected SMA: Order urgent SMN1 gene deletion testing immediately, as early diagnosis is critical for disease-modifying therapies 2
• Full mutation characterization is mandatory to determine reading frame effects, predict disease progression, and establish eligibility for mutation-specific therapies 3

Advanced Diagnostic Tools

Muscle Biopsy:

• Only perform if genetic testing is negative or inconclusive 3
• Use EMG to identify the weakest muscle, then biopsy the contralateral side to maximize diagnostic yield 4

MRI Imaging:

• T2-weighted sequences with fat suppression (STIR) can confirm muscle edema and inflammation without invasive testing 4
• Particularly useful in children to avoid EMG or biopsy 4

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Treatment Framework by Etiology

Duchenne Muscular Dystrophy

Pharmacological Management:

• Initiate glucocorticoids between ages 4-6 years when motor skills plateau or decline: prednisone/prednisolone 0.75 mg/kg daily OR deflazacort 0.9 mg/kg daily 1
• These are the only medications proven to slow decline in muscle strength and function 1
• Start cardiac protection early: ACE inhibitors and beta-blockers should be initiated at the first sign of cardiac dysfunction, even if asymptomatic 1

Monitoring Protocol:

• Cardiac: Baseline echocardiogram at diagnosis or by age 6, then every 24 months until age 10, then annually 1
• Respiratory: Pulmonary function testing every 6 months measuring FVC, MIP/MEP, and peak cough flow 1
• Neuromuscular function: Manual muscle testing and timed function tests (10-meter walk, timed Gowers, 4-stair climb) every 6 months during ambulatory phase 1

Respiratory Intervention:

• Initiate noninvasive ventilation (NIV) when FVC declines, MIP/MEP reduces, overnight oximetry becomes abnormal, or polysomnography shows sleep-disordered breathing 1
• Respiratory failure is the leading cause of mortality in neuromuscular disease 1

Spinal Muscular Atrophy

Disease-Modifying Therapies:

• Risdiplam (EVRYSDI) is FDA-approved for SMA in pediatric and adult patients 5
• Dosing by age/weight:
  • <2 months: 0.15 mg/kg daily
  • 2 months to <2 years: 0.2 mg/kg daily
  • ≥2 years and <20 kg: 0.25 mg/kg daily
  • ≥2 years and ≥20 kg: 5 mg daily 5
• Critical timing: All three available SMA therapies (nusinersen, onasemnogene abeparvovec, risdiplam) are most effective when given before symptom development or as early as possible after symptom onset 6
• Newborn screening allows diagnosis and treatment initiation before irreversible motor neuron loss 7

Pompe Disease

Physical Therapy Approach:

• Enhance muscle function through submaximal, functional, and aerobic exercise 4
• Avoid excessive resistive and eccentric exercise to prevent overwork weakness 4
• Balance activity with rest: Provide practice and gentle strengthening within physiological limits, avoiding both overexertion and disuse atrophy 4

Musculoskeletal Management:

• Prevent contractures through stretching, positioning, orthotic intervention, and splinting 4
• Monitor bone health with DEXA scans for osteopenia/osteoporosis 4
• Assess scoliosis, hip stability, and long bone integrity with radiographs as needed 4

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Universal Management Principles

Orthopedic Interventions

• Prescribe ankle-foot orthoses when ankle dorsiflexion weakness develops to prolong ambulation 1
• Consider surgical intervention (iliotibial band lengthening, Achilles tendon release) when contractures limit function 1

Psychosocial Support

Cognitive and Behavioral Assessment:

• Perform comprehensive neuropsychological testing at diagnosis and before school entry 1
• Screen regularly for depression, anxiety, obsessive-compulsive disorder, and ADHD 4, 1
• Neurodevelopmental risks in DMD: Increased rates of autism spectrum disorders, attention-deficit disorder, language delays, and specific learning disorders 4

Educational Planning:

• Develop individualized education plans for all children with muscular atrophy to address learning problems, modify harmful physical activities, and ensure accessibility 4

Family Support:

• Designate a care coordinator with neuromuscular disease expertise to serve as the family's point of contact 4, 1
• Provide parent-to-parent support, which families report as one of the most valued resources 4
• Screen parents and siblings for depression and adjustment difficulties, as parental depression rates are elevated 4

Multidisciplinary Team

Essential specialists include: neurology, cardiology, pulmonology, physical therapy, occupational therapy, speech therapy, nutrition, psychology, and genetics 1

Palliative Care Integration

• Integrate palliative care early for pain management, emotional/spiritual support, and guidance with treatment decisions 1
• This approach improves quality of life and may prolong survival 1

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Critical Pitfalls to Avoid

• Never attribute persistently elevated CK to exercise alone in young children—in DMD, CK remains permanently high (>10,000 U/L) and does not show temporary fluctuations 3
• Do not delay genetic testing while waiting for muscle biopsy results, as genetic testing should be performed immediately from blood samples 3, 1
• Do not miss the therapeutic window for SMA: Disease-modifying therapies are most effective before symptom onset or as early as possible, as motor neuron loss is irreversible 2, 6, 7
• Do not overlook cardiac involvement: Start cardiac monitoring and protective medications early, even before symptoms develop 1
• Avoid excessive resistive exercise in progressive muscle diseases, as this can cause overwork weakness 4