A 5‑month‑old infant with delayed motor milestones, good feeding, generalized hypotonia, mildly preserved reflexes, weak antigravity muscle strength, no fasciculations, normal creatine kinase level, and electromyography showing a myopathic pattern—what is the most likely diagnosis?

Diagnosis: Congenital Myopathy (Answer B)

The most likely diagnosis is congenital myopathy based on the combination of hypotonia with preserved reflexes, normal CK, and myopathic EMG pattern in this 5-month-old infant. 1, 2, 3

Key Diagnostic Features Supporting Congenital Myopathy

Normal Creatine Kinase is Decisive

• Normal CK essentially rules out congenital muscular dystrophy (option D), which typically presents with markedly elevated CK levels often exceeding 1000 U/L. 1, 2, 3
• Normal CK is the hallmark feature of most congenital myopathies including nemaline myopathy, central core disease, and centronuclear myopathy. 3
• This single laboratory finding is the most powerful discriminator between congenital myopathy and congenital muscular dystrophy. 1, 2

Preserved Reflexes Exclude Neurogenic Disorders

• Preserved reflexes effectively rule out spinal muscular atrophy (option C), which characteristically presents with diminished or absent deep tendon reflexes due to anterior horn cell loss. 2, 3
• The absence of fasciculations further supports a primary muscle disorder rather than anterior horn cell disease like SMA. 2, 3
• Hypotonia with preserved reflexes is the classic presentation pattern that directs investigation toward primary muscle disorders. 2, 3

Preserved Reflexes Also Exclude Cerebral Palsy

• Cerebral palsy (option A) is ruled out because it presents with spasticity, increased muscle tone, and hyperreflexia as an upper motor neuron disorder. 2, 3
• The hypotonia and preserved (not increased) reflexes in this patient are incompatible with cerebral palsy. 1, 2
• EMG does not show a myopathic pattern in cerebral palsy. 1

Clinical Pattern Characteristic of Congenital Myopathy

The Classic Triad

• The combination of hypotonia, weak antigravity muscle power, and preserved reflexes with myopathic EMG strongly supports congenital myopathy. 3
• Congenital myopathies are defined by "hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course." 2, 3, 4
• Good feeding ability suggests relatively preserved bulbar function, which is consistent with many congenital myopathy subtypes. 2

EMG Confirmation

• The myopathic EMG pattern—characterized by polyphasic motor unit action potentials of short duration and low amplitude with increased insertional activity—confirms a primary muscle disorder rather than a neurogenic process. 1
• EMG showing myopathy with normal CK is the classic presentation of congenital myopathy. 3

Next Steps for Definitive Diagnosis

Muscle Biopsy is Essential

• Muscle biopsy remains the gold standard for confirming congenital myopathy diagnosis and identifying the specific subtype through characteristic structural abnormalities including nemaline rods, central cores or minicores, central nuclei, and type 1 fiber predominance. 1, 2, 3
• The diagnosis of a specific congenital myopathy should only be made when the defining morphologic feature is the predominant pathologic change. 5

Genetic Testing Follows Biopsy

• Genetic testing should follow muscle biopsy findings, with RYR1 mutations being the most common cause, and can identify causative mutations in over 15 different genes associated with congenital myopathies. 1
• Next-generation sequencing is increasingly used given the unexpectedly wide genetic and clinical heterogeneity of these disorders. 6, 4

Critical Management Considerations

Immediate Actions Required

• Immediate referral to pediatric neurology or genetics for muscle biopsy is indicated to determine the specific congenital myopathy subtype and guide prognosis. 2, 3
• Concurrent referral to early intervention services should proceed while diagnostic workup continues. 2, 3
• Cardiac evaluation should be performed, as certain congenital myopathy subtypes can develop cardiomyopathy and arrhythmias. 2, 3

Respiratory Monitoring

• Regular monitoring of respiratory muscle weakness is necessary, even when limb weakness appears mild or static, due to the risk of nocturnal hypoventilation. 1
• This is particularly important with certain genetic subtypes such as SEPN1 mutations and nemaline myopathy. 1