SMA

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by degeneration of motor neurons in the spinal cord and brainstem, leading to progressive muscle weakness and atrophy. It is caused mainly by homozygous deletions or mutations in the SMN1 gene on chromosome 5, which reduces production of the survival motor neuron (SMN) protein essential for motor neuron survival. The clinical severity is influenced by the number of SMN2 gene copies, a nearly identical gene that mostly produces a nonfunctional SMN protein; more SMN2 copies tend to correlate with a milder course.

SMA is inherited in an autosomal recessive pattern. It occurs in about 1 in 6,000 to 10,000 live births, with a carrier frequency of roughly 1 in 40. Disease onset and progression vary and are commonly categorized by age of onset and walking ability: Type 1 presents in infancy with severe hypotonia and respiratory problems and usually never sits or walks; Type 2 begins in infancy to early childhood, with sitting but often not walking; Type 3 begins in childhood or adolescence with the ability to walk but progressive weakness; Type 4 begins in adulthood with milder symptoms.

Diagnosis is confirmed by SMN1 genetic testing and assessment of SMN2 copy number; newborn screening is implemented in some regions. Treatments include disease-modifying therapies: nusinersen (Spinraza), an antisense oligonucleotide; risdiplam (Evrysdi), an oral SMN2 splicing modifier; and onasemnogene abeparvovec-xioi (Zolgensma), a one-time gene therapy. Supportive care such as respiratory support, nutrition management, and physical therapy remains important. Early diagnosis and access to therapy improve outcomes and survival.