Group of autosomalrecessivemotor neuron disorders (SMN1 gene deletion on 5q) causing degeneration of anterior horn cells and progressive symmetric muscle weakness/atrophy (proximal > distal).
SMA is the second most common fatal AR disorder after cystic fibrosis, making it a leading genetic cause of infant mortality. However, newly available therapies (e.g., SMN-enhancing nusinersen) can dramatically improve survival if started early.
Type 0 (very rare, congenital): ↓fetal movements, arthrogryposis, and facial weakness in utero; infant born with severe hypotonia and respiratory failure (usually fatal within months).
Type I (infantile, Werdnig-Hoffmann): onset <6 mo with floppy baby hypotonia, poor head control, tongue fasciculations, weak suck/swallow, and breathing difficulties; without intervention most die <2 yrs.
Type II (intermediate, Dubowitz): onset 6–18 mo; infants can sit but never stand or walk; symmetric flaccid weakness (legs > arms) with absent reflexes; progressive scoliosis and respiratory issues, survival often into young adulthood.
Type III (juvenile, Kugelberg-Welander): onset >18 mo (toddler/childhood); walks initially but may lose ambulation later; proximal leg weakness (difficulty running, climbing) is most prominent; no significant respiratory issues and near-normal life expectancy.
Type IV (adult-onset): onset in the 20s–30s with very mild proximal muscle weakness; slow progression and normal lifespan (may resemble a pure lower motor neuron form of ALS).
Suspect SMA in an infant with hypotonia and areflexia (especially if tongue fasciculations) – confirm diagnosis with genetic testing (SMN1 deletion analysis), which is now included in newborn screening.
Differentiate SMA vs muscle disorders: in SMA, creatine kinase levels are normal or mildly ↑ (due to neuron loss), whereas muscular dystrophies show very high CK.
Electrodiagnostics (EMG/NCS): normal nerve conduction with diffuse denervation on EMG supports a motor neuron process (vs primary muscle or peripheral nerve pathology).
If family history is positive, consider prenatal testing (CVS or amniocentesis) to detect SMA in utero.
X-linked myopathy; onset ~2–3 yrs (not neonatal) with proximal weakness, calf pseudohypertrophy, and ↑↑CK
Congenital myopathy
floppy infant due to intrinsic muscle disorders (e.g., central core, nemaline); often milder or static course; normal or mildly ↑CK
Infantile botulism
floppy baby with constipation and cranial nerve palsies (C. botulinum toxin from honey blocks ACh release at NMJ)
Disease-modifying therapies: Nusinersen (antisense oligo ↑SMN2-derived protein, intrathecal), Risdiplam (oral SMN2 splicing modifier), and Onasemnogene abeparvovec (one-time gene replacement) – these can improve motor function, especially if started early.
Supportive care: multidisciplinary support with PT/OT (maximize motor function, prevent contractures), respiratory support (e.g., BiPAP or ventilation), and nutritional support (feeding tube if risk of aspiration).
More SMN2 gene copies → milder SMA (extra SMN2 backup genes produce more functional protein).
Tongue fasciculations in a floppy infant are a red flag for SMA (LMN lesion).
Respiratory failure – Paradoxical breathing (bell-shaped chest) or hypoventilation in an SMA infant signals impending failure; initiate ventilatory support immediately.
Aspiration risk – Poor swallowing and weak cough can cause aspiration pneumonia; provide feeding support (NG/PEG tube) to prevent this.
Positive newborn screen or 'floppy' infant → confirm SMA with SMN1 genetic test.
If SMA confirmed → promptly begin SMN-enhancing therapy (e.g., nusinersen) before significant motor neuron loss occurs.
