Adaptive functioning in school-aged children with spinal muscular atrophy in the treatment era: a non-randomised cohort study.

Farah, Emily E; Paguinto, Sarah-Grace; Mandarakas, Melissa R; Herbert, Karen; Krishan, Smriti; Sampaio, Hugo; Kariyawasam, Didu S; Farrar, Michelle A · Lancet Reg Health West Pac · 2026

prospective_cohort · Level II

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Abstract

Despite diagnostic and therapeutic advances for spinal muscular atrophy (SMA), long-term outcomes focused on functional independence for children have not been explored. This study aimed to characterise adaptive functioning for affected children within the contemporary SMA treatment paradigm. This prospective, non-randomised Australian cohort study was conducted from January 1 to November 14 2025 and included children with SMA aged 4-12 years, diagnosed and treated through newborn screening (NBS) or clinical referral (CR). Adaptive functioning was primarily assessed using the Pediatric Evaluation of Disability Inventory Computer Adaptive Test. Thirty-nine children participated (NBS n = 18, CR n = 21) with median treatment duration of 67.3 months (IQR 54.0-85.0). Children had high levels of participation with scores within expected range for age-matched peers for social/cognitive (38/39, 97%), responsibility (35/39, 90%), daily activities (29/39, 74%) and mobility (16/39, 41%) domains. A greater proportion of children identified through NBS achieved expected scores for all domains compared to children diagnosed through CR (NBS 14/18 (78%), CR 2/21 (10%), p < 0.001). All children diagnosed through NBS with 3 survival motor neuron 2 gene (<i>SMN2</i>) copies achieved expected scores for all domains (3 <i>SMN2</i> 7/7 (100%), 2 <i>SMN2</i> 7/11 (64%)). Children diagnosed through CR with higher functional status at diagnosis reported greater frequency of daily activities scores within expected range (walkers 7/7 (100%), sitters 2/5 (40%), non-sitters 3/9 (33%), p = 0.02). Whilst heterogenous in terms of performance-based measures, children with SMA have collective strengths in social-cognitive and responsibility aspects of adaptive functioning. Early diagnosis and treatment through NBS and <i>SMN2</i> copy number are important modifiers of long-term adaptive functioning, providing evidence for individualized goal-setting, monitoring and multidisciplinary care. National Health and Medical Research Council Investigator Grant (1194940, 2026317), University of New South Wales (UGCA1064).