What is the likely diagnosis for a 6-week-old child with normal eye fixation, weak anti-gravity movement, normal Creatine Kinase (CK) levels, and decreased reflexes?

Diagnosis: Spinal Muscular Atrophy (SMA)

The most likely diagnosis for this 6-week-old infant with weak anti-gravity movements, decreased reflexes, and normal CK is Spinal Muscular Atrophy (SMA), specifically Type 1 (Werdnig-Hoffmann disease).

Clinical Reasoning

Key Distinguishing Features

The combination of decreased reflexes with hypotonia in early infancy is pathognomonic for lower motor neuron disease, specifically SMA 1. This clinical presentation creates a clear diagnostic pathway:

• Diminished or absent deep tendon reflexes occur with lower motor neuron disorders, distinguishing them from upper motor neuron dysfunction which shows increased reflexes 1
• Normal eye fixation effectively rules out severe congenital myopathies that typically present with ophthalmoplegia or significant ocular motor dysfunction 2, 3
• Normal CK essentially excludes muscular dystrophies (including DMD and congenital muscular dystrophies), which characteristically show CK elevations often >1000 U/L 1, 2, 3

Why Not Congenital Myopathy?

While congenital myopathies can present with hypotonia and weakness in early infancy, several features argue against this diagnosis:

• Congenital myopathies typically preserve or show normal to slightly decreased reflexes, not the markedly decreased reflexes seen in this case 2, 3
• Hypotonia with preserved reflexes is the classic presentation of congenital myopathy, whereas this patient has decreased reflexes 2, 3
• The American Heart Association states that congenital myopathies are characterized by "hypotonia with preserved reflexes" as a distinguishing feature from neurogenic causes 3

Why Not DMD?

DMD is effectively excluded by multiple factors:

• DMD typically presents at 2-4 years of age, not at 6 weeks 1
• CK concentration is significantly elevated in DMD, usually >1000 U/L, whereas this patient has normal CK 1
• The age of presentation is far too early for DMD manifestation 1

SMA Type 1 Clinical Profile

SMA Type 1 presents in the first 6 months of life with profound weakness, hypotonia, and absent or markedly diminished reflexes 1. Critical diagnostic features include:

• Absence of fasciculations on examination supports but does not exclude SMA, as tongue fasciculations may be subtle or missed in young infants 1
• Weak anti-gravity movements at 6 weeks with decreased reflexes is the hallmark presentation of early-onset SMA 1
• Normal eye movements are characteristic of SMA, as extraocular muscles are typically spared 2

Critical Diagnostic Pitfall

The absence of observed tongue fasciculations should not dissuade from the diagnosis of SMA, as these can be difficult to detect in young infants and may require careful, repeated examination 1. The combination of age, decreased reflexes, and normal CK makes SMA the overwhelming diagnostic probability.

Immediate Next Steps

• Urgent genetic testing for SMN1 gene deletion is the definitive diagnostic test and should be ordered immediately 1
• Early diagnosis is critical as disease-modifying therapies (nusinersen, onasemnogene abeparvovec) are most effective when initiated early in the disease course
• Referral to pediatric neurology should occur concurrently with genetic testing 3