Rossella D'Alessandro, Francesca Re, Martina Vacchetti, Francesca Sertori, Luca Arletti, Alice Campagna, Giulio Gadaleta, Tiziana Enrica Mongini, Federica Silvia Ricci
Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by out-of-frame variants in the DMD gene, resulting in dystrophin deficiency and progressive muscle degeneration. Beyond motor involvement, evidence links DMD to cognitive impairment and an emotional-behavioral (EB) burden, potentially related to the altered expression of brain dystrophin isoforms (Dp71, Dp140, Dp427). Objectives: To screen for major neurodevelopmental, cognitive and/or EB difficulties in a monocentric cohort of children with DMD. Methods: This cross-sectional study included 21 children with DMD. Neuropsychiatric difficulties were assessed using a multimodal psychometric battery. Cognitive, neurodevelopmental and genetic data were retrospectively collected and analyzed. Results: In the cohort, attention-deficit/hyperactivity disorder (ADHD)-related findings were predominantly inattentive, with 3/20 children (15.0%) scoring within the clinical range on at least one inattention subscale. For measures assessing autism spectrum disorder (ASD)-related features, scores above the normative cutoff emerged in 7/20 children (35.0%), while only 2/20 (10.0%) scored within the clinical range. Internalizing problems represented the predominant EB difficulties, and emotional dysregulation (ED) emerged as a plausible area of vulnerability in the cohort. Among the 11 of 21 children with available Full-Scale Intelligence Quotient (FSIQ) data, five (45.5%) had an FSIQ below 85. Of these, four of five (80.0%) presented the predicted Dp140-/Dp71+ brain dystrophin isoform expression pattern, whereas one of five (20.0%) presented the Dp140+/Dp71+ pattern. Conclusions: Children with DMD showed heterogeneous neuropsychiatric and cognitive features in the employed screening battery. These preliminary findings, if confirmed in larger cohorts, support the potential of a broader neuropsychiatric screening assessment to optimize care pathways.