Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome (EPSA-DSMA) is a rare, inherited neurological disorder characterized by progressive intellectual disability, spasticity, ataxia, and distal muscle weakness. It is caused by mutations in the SETX gene, which is responsible for producing the enzyme senataxin. This enzyme is involved in the repair of DNA damage and in the regulation of gene expression. Symptoms typically begin in early childhood and worsen over time. Treatment is supportive and may include physical therapy, occupational therapy, speech therapy, and medications to manage symptoms.