Intellectual disability and genotype-phenotype correlation between full-scale intelligence quotient and mutation characteristics in boys with dystrophinopathy.

BACKGROUND: Neuropsychological evaluations of dystrophinopathy patients indicate a decrease in mean full-scale intelligence quotient (FSIQ) compared to the general population. However, large-scale studies with longitudinal follow-up in this regard are yet to be conducted in the Indian subcontinent.

METHODS: Verbal, performance, and FSIQ of children with dystrophinopathy, aged 6-16 years were prospectively compared with age/socioeconomic status matched healthy controls, using the Malin's Intelligence Scale for Indian children (MISIC). Additionally, cognitive assessments were repeated in dystrophinopathy boys who completed at least one year of follow-up during study period. Genotype-phenotype correlation was also explored between FSIQ and mutational characteristics by dividing the dystrophinopathy group into Dp427, Dp140, and Dp71 isoforms. Furthermore, other clinical/genetic predictors of cognitive status were explored in dystrophinopathy cases.

RESULTS: A total of 154 and 77 boys were enrolled in the dystrophinopathy and control groups, respectively. While the dystrophinopathy group had lower scores in verbal, performance, FSIQ, and all sub-tests compared to the control group (p < 0.001), their performance IQ was paradoxically better than verbal IQ (86.9 ± 12.3 vs 83.6 ± 11.4, p = 0.008). The Dp71 group had significantly lower verbal, performance, and FSIQ, and this isoform was found to be an independent predictor of intellectual disability in the dystrophinopathy group in multivariate analysis. Follow-up IQ assessment after one year (n = 47) showed a non-significant reduction in FSIQ (85.1 ± 10.7 vs 84.3 ± 11.2, p = 0.64).

CONCLUSION: Boys with dystrophinopathy exhibit lower IQ compared to healthy controls, and the degree of cognitive impairment is more pronounced in cases with the Dp71 isoform.