Investigating Genetic, Cognitive, and Therapeutic Approaches for Enhancing Quality of Life in Individuals With Down Syndrome

Abstract

Background: Down syndrome (DS) is associated with substantial heterogeneity in cognition, adaptive functioning, and behavior, influenced by cytogenetic subtype and modifiable rehabilitative exposures, yet integrated regional evidence from South Punjab remains limited. Objective: To evaluate associations between cytogenetic subtype, therapy dose and modality, and standardized cognitive, adaptive, and behavioral outcomes among individuals with DS. Methods: A cross-sectional observational study was conducted in South Punjab (January–March 2025) including 60 individuals with cytogenetically confirmed DS aged 6–35 years. Cognitive performance was assessed using WISC-IV/WAIS-IV, adaptive functioning via VABS-II, and behavioral symptoms via the Aberrant Behavior Checklist. Therapy exposure over the preceding 6 months was operationalized as weekly minutes and categorized by intensity; modality was classified as single-modality versus multidisciplinary. Analyses used correlations, group comparisons, and multivariable linear regression (SPSS v26; α=0.05). Results: Full trisomy 21 occurred in 88.3%, mosaicism in 8.3%, and translocation in 3.4%. Mean Full-Scale IQ was 48.3±9.7, higher in mosaicism than trisomy 21 (56.2±6.4 vs 47.5±8.9; p=0.03). VABS-II composite averaged 62.8±11.3 and correlated with IQ (r=0.56; p<0.001). Multidisciplinary therapy was associated with higher VABS-II scores than single-modality therapy (67.2±9.8 vs 58.9±10.4; p=0.001; d=0.89). In regression, therapy intensity (β=0.42; p=0.002) and IQ (β=0.38; p=0.005) independently predicted adaptive functioning (adjusted R²=0.44). Conclusion: Adaptive outcomes in DS are more strongly associated with therapy intensity and multidisciplinary rehabilitation than cytogenetic subtype alone, supporting scalable integrated intervention models in resource-constrained settings.