This current study investigates the potential utility of pre-confirmatory electrodiagnostic (EDx) testing—specifically compound muscle action potential (CMAP) amplitudes—in predicting SMN2 copy number and severity of  disease in spinal muscular atrophy (SMA) newborns identified through newborn screening (NBS), with the aim of supporting timely therapeutic decisions.

NBS enables SMA detection before symptom onset, allowing early gene therapy initiation. However, confirmatory genetic testing often takes time; potentially delaying treatment authorization which is critical for affected patients. Early EDx tests may bridge this gap by providing objective and rapid evidence of motor neuron integrity and disease severity.

This observational cohort included 21 NBS-positive SMA neonates with recorded CMAP amplitudes (right sided; median-abductor pollicis brevis (APB), ulnar-abductor digiti minimi amplitudes (ADM), and fibular-tibialis anterior (TA) nerves). Seven (33%) infants  underwent EMG before genetic confirmation at a median age of 13 days. Six of these (85%) were later confirmed to have two-SMN2 copies. Pre-confirmatory EMG results were compared with post-confirmatory EMG findings among patients with two- versus three-SMN2 copies.

Pre-confirmatory EMG offers an early, clinically meaningful objective measure of motor neuron loss associated with SMN2 copy number and disease severity in NBS-positive pre-symptomatic SMA babies. EMG/EDx integration into early SMA assessment can help families and caregivers acknowledge disease severity in otherwise well appearing newborn SMA babies (i.e. point of care technology).