Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening.

Objective: Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown.

Methods: 40 of 47 eligible SMA patients (23 females/17 males) from 39 families identified through newborn screening between January 2018 and December 2020 underwent developmental testing using Bayley III (BSID) after the 2 years of age. The mean age was 29.25 months (23-42 months). 17 patients had 2, 11 patients had 3 and 12 patients had ≥4 copies of SMN2.

Results: cognitive scale: mean 94.55 (SD 24.01); language scale: mean 86.09 (SD 26.41); motor scale: 81.28 (SD 28.07). Overall, the cognitive scales show that 14 children were below average, 20 children were average and 6 children were above average. 10/14 children with below average scores had 2 SMN2 copies. The post-hoc pairwise comparisons showed that the cognition main scale was significantly more sensitive to the number of SMN2 copies than the motor main scale of the BSID (MΔ= 10.27, p = 0.014). There is also evidence that cognition scored higher than the language main scale (MΔ= 7.11, p = 0.090).

Conclusion: The impaired cognitive development of SMA children with 2 SMN2 copies, despite early initiation of therapy, underscores the critical role of the SMN protein in the early stages of brain development.