Swallowing development in infants and toddlers with spinal muscular atrophy following therapy compared to healthy controls: the prospective controlled DySMA trial

TL;DR

This study compares swallowing development in infants and toddlers with spinal muscular atrophy and healthy controls, showing how early treatment and genetic factors influence outcomes.

Contribution

The study introduces a controlled comparison of swallowing development in SMA patients and healthy controls, highlighting the impact of treatment timing and SMN2 copy number.

Findings

Children with SMA showed significantly different swallowing development trajectories compared to healthy controls.

Presymptomatic treatment led to early swallowing progress similar to healthy controls but declined after 15–17 months.

Higher SMN2 copy number was associated with better early swallowing development resembling healthy controls.

Abstract

Swallowing development is a crucial outcome measure for evaluating the effectiveness of disease-modifying therapies (DMT) in children with spinal muscular atrophy (SMA). However, data on this aspect remain limited due to a lack of assessment tools. This study aimed to evaluate swallowing development in infants and toddlers with SMA, compare it with healthy controls (HC), and investigate the influence of initial symptom status at start of DMT and SMN2 copy number.

An observational study was conducted with infants and toddlers diagnosed with SMA at a single neuropediatric center and a HC group. Swallowing development was primarily assessed using the DySMA scale. Group differences and the impact of initial symptom status and SMN2 copy number on swallowing were analyzed using linear mixed-effects models.

The study included 127 infants and toddlers, 35 with SMA (0–36 months, 19 girls), who started DMT either presymptomatically (n = 18) or symptomatically (n = 17), with two (n = 26) or three (n = 9) SMN2 copies, predominantly receiving Onasemnogene abeparvovec alone (n = 26), and a healthy control group (n = 92, 0–23 months, 34 girls). Children with SMA displayed significantly different swallowing development trajectories (-0.06 DySMA points by months of life, p=.06; 95% CI -0.13 to 0.01) compared to HC (+ 0.45 DySMA points by months of life, p<.01, 95% CI 0.25 to 0.65). Notably, those treated presymptomatically demonstrated swallowing progress comparable to HC up to 15–17 months but experienced a decline thereafter (18–24 months; β = 8.22, p<.001; 95% CI 4.20 to 12.26). The group with three SMN2 copies exhibited a developmental pattern similar to HC up to the age of 24 months.

Higher SMN2 copy number and presymptomatic DMT initiation were associated with similar early swallowing development compared to HC. Long-term studies stratifying swallowing development by SMN2 copy number are warranted.

The online version contains supplementary material available at 10.1186/s13023-026-04227-3.

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