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Assessment of adaptive functioning in Angelman syndrome using the Vineland Adaptive Behavior Scales, Third Edition

Potter, S. N.; Zhang, J.; Friedman, B.; Gable, J.; Ali, N.; Barbieri-Welge, R. L.; Ben-Tall, A.; Caravella, K. E.; DeRamus, M.; Garic, D.; MacKay, M.; Murias, K.; Peters, S. U.; Smyth, K.; Summers, J.; Wang, A.; Shen, M. D.; Hipp, J. F.; Tillmann, J.; Tjeertes, J.; Vincenzi, B.; Bird, L. M.; Tan, W.-H.; Wheeler, A. C.; Sadhwani, A.

2026-06-22 genetic and genomic medicine
10.64898/2026.06.11.26355399 medRxiv
Show abstract

Purpose: This study examined longitudinal trajectories of adaptive functioning in 331 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) and examined differences by molecular subtype. Methods: A total of 331 individuals (156 females, 47%) with genetically confirmed AS (ages 6 months to 52 years) were assessed between 2018 and 2025, including 207 with a deletion subtype, 63 with uniparental disomy or imprinting defect, and 61 with a UBE3A point mutation. Growth scale values were analyzed using linear mixed-effects models with log2-transformed age. Results: Individuals with deletion subtypes demonstrated significantly lower adaptive functioning across domains compared to those with non-deletion subtypes. Adaptive skills across all Vineland-3 subdomains increased nonlinearly with age, showing faster growth early in life that slowed over time, with largely parallel trajectories across subtypes. Conclusion: Individuals with AS demonstrate slow but steady growth in adaptive functioning that continues into adulthood, with progress varying by molecular subtype. These findings provide updated natural history benchmarks and demonstrate the utility of the Vineland-3 for clinical trials.

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