The Role of Dystrophin Gene Mutations in Neuropsychological Domains of DMD Boys: A Longitudinal Study

Abstract

Background: Duchenne Muscular Dystrophy (DMD) is a fatal muscular dystrophy of pediatric population coupled with other secondary comorbidities including mental retardation and neuropsychological impairments. Mutation location in the dystrophin gene, have been associated with neuropsychological functioning in DMD. Purpose: We investigated temporal changes in the neuropsychological functioning of DMD subjects, hitherto understudied. Methods: Subjects with suspected DMD were enrolled according to the ethical guidelines. Genetic confirmation by Multiplex Ligation Dependent Probe Amplification was carried out to identify pathogenic deletion or duplication in dystrophin gene. Intellectual and neuropsychological functioning was assessed by using standardized batteries. Investigated neuropsychological domains included visual, verbal and working memory, selective and sustained attention, executive functioning, verbal fluency, and visuo-constructive and visuo-spatial abilities. The assessments were carried out at baseline and followed for one time point in 30 cases. Result: The follow-up assessment revealed that neuropsychological functioning did not worsen with time. Improvements were seen in block designing task ( p = 0.050), serial positioning primacy effect ( p = 0.002), Stroop incongruent task ( p = 0.006), visual long-term memory ( p = 0.003) and attention ( p = 0.001). DMD cases with mutation location affecting short dystrophin isoform (Dp140) also showed improvement in these domains. Conclusion: No temporal alterations were found in DMD subjects, though improvements in few domains were observed. Neuropsychological rehabilitation may be useful in improving the quality of life in DMD subjects.

A Longitudinal Follow-Up Study of Intellectual Function in Duchenne Muscular Dystrophy over Age: Is It Really Stable?

“…This cross-sectional study also reported, for the first time, that cognitive quotients and pattern of functioning showed no change with age. These findings have subsequently been confirmed in other cohorts [ 2 , 3 , 4 , 5 ] and the assumption that cognitive function does not change over time has become commonly accepted. Hellebrekers et al [ 6 ] reported a longitudinal follow-up study on verbal span and processing speed in Duchenne boys and found a developmental stagnation in verbal-span capacity, irrespective of normal processing speed, appearing more pronounced in patients missing Dp427 and Dp140.…”

“…Several cross-sectional studies have previously reported that cognitive function does not significantly change over time [ 2 , 3 , 4 , 5 ]. Longitudinal assessments in our cohort confirm that the mean changes in a large cohort of 70 DMD boys was relatively small (−2.99 points).…”

“…Hellebrekers et al [ 6 ] reported a longitudinal follow-up study on verbal span and processing speed in Duchenne boys and found a developmental stagnation in verbal-span capacity, irrespective of normal processing speed, appearing more pronounced in patients missing Dp427 and Dp140. The concomitant involvement of Dp71 increases the risk of cognitive impairment and associated psychiatric comorbidities [ 3 , 4 , 5 ].…”

Computational cognitive modeling and validation of Dp140 induced alteration of working memory in Duchenne Muscular Dystrophy

“…Studies report deficits in verbal intelligence quotient 12 as a part of general intelligence and non-verbal memory, executive functions 13 , attention, visuo-construction ability 14 , problems with narrative, linguistic and reading skills 15 . We have also reported a non-progressive deterioration of neuropsychological domains 16 . Conflicting and variable degree of cognitive output in DMD necessitates understanding of a common cognitive domain for designing rehabilitation strategies 17 .…”

Working Memory Alterations Plays an Essential Role in Developing Global Neuropsychological Impairment in Duchenne Muscular Dystrophy

“…The presence of non-progressive mental retardation is a prominent clinical feature in DMD ( Bresolin et al, 1994 ). We have also reported non-progressive intellectual and neuropsychological deficits in our DMD cohort ( Tyagi et al, 2019b ).…”