Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene, resulting in deficiency of survival motor neuron (SMN) protein. SMN protein is essential for survival and function of motor neurons in the anterior horn of the spinal cord. Without adequate SMN, motor neurons degenerate, causing progressive muscle weakness and atrophy beginning proximally (hip and shoulder muscles) and advancing distally. Type 1 SMA presents before age 6 months with severe hypotonia, poor head control, and inability to sit independently; without intervention, respiratory failure and death occur by age 2. Type 2 presents with later onset, and affected children can sit but not walk independently. Type 3 presents after age 18 months; affected individuals can walk but with progressive decline. The transformative FDA approval of nusinersen (Spinraza), a gene therapy (zolgensma), and more recently risdiplam (Evrysdi) has dramatically changed SMA outcomes, allowing many Type 1 patients to achieve developmental milestones previously thought impossible.