Spinal Muscular Atrophy

Abstract

ABSTRACT OBJECTIVE This article provides a comprehensive overview of the diagnostic assessment and treatment of individuals with spinal muscular atrophy (SMA) due to homozygous deletions of SMN1. LATEST DEVELOPMENTS In recent years, most states have incorporated SMA in their newborn screening panel. To provide the earliest diagnosis possible after symptom onset, vigilance is needed for births in states without newborn screening for SMA and when compound heterozygotes are missed by newborn screening programs. Supportive care for respiratory, nutritional, and orthopedic health impacts outcomes and is the cornerstone of care. Adaptive equipment, including assistive home technology, enables affected individuals to gain autonomy in their daily activities. Pharmacologic treatments approved by the US Food and Drug Administration (FDA) include three drugs that increase deficient survival motor neuron protein levels through SMN1- or SMN2- directed pathways: nusinersen, onasemnogene abeparvovec, and risdiplam. Efficacy for these trials was measured in event-free survival (survival without the need for permanent ventilation) and gains in functional motor outcomes. Earlier treatment is most effective across all treatments. ESSENTIAL POINTS The diagnostic and therapeutic landscapes for SMA have seen dramatic advancements in recent years, improving prognosis. Optimized supportive care remains essential, and vigilance is needed to define the new natural history of this disease.