Cognitive and neurodevelopmental outcomes in spinal muscular atrophy: a scoping review

Spinal muscular atrophy (SMA) has traditionally been described as a motor neuron disorder; however, increasing evidence suggests a broader neurodevelopmental involvement, particularly in the era of disease-modifying therapies. As survival and motor outcomes improve, cognitive and behavioral trajectories have become clinically relevant but remain inconsistently characterized. To systematically synthesize current evidence on cognitive and neurodevelopmental outcomes in children and adults with SMA, with particular focus on differences across phenotypes and therapeutic eras. A scoping review was conducted including observational studies, clinical cohorts, and case series reporting cognitive, language, behavioral, or executive outcomes in individuals with SMA. Studies were analyzed qualitatively with attention to disease severity, age, and treatment status. Twenty-three studies were included. Global intellectual functioning was generally preserved, particularly in SMA types II and III. Nevertheless, selective vulnerabilities were frequently reported in processing speed, executive functioning, and language development. Behavioral and socio-emotional challenges were described in pediatric populations. Neurodevelopmental outcomes in early-onset SMA showed substantial heterogeneity, ranging from global developmental delay to relatively preserved cognitive trajectories, especially in pre-symptomatically treated patients. Methodological variability and motor-related testing limitations were common across studies. Cognitive functioning in SMA appears largely preserved in milder phenotypes but domain-specific vulnerabilities in processing speed, working memory, and language are consistently identified across phenotype groups and represent clinically relevant targets for monitoring and intervention. Systematic neurodevelopmental monitoring and standardized assessment protocols are needed to better define long-term outcomes as treatment modifies disease trajectories.