Relationships between <i>DMD</i> mutations and neurodevelopment in dystrophinopathy.

Abstract

We performed a prospective, cross-sectional analysis of neurodevelopmental concerns and psychosocial adjustment in relation to <i>DMD</i> mutations in young steroid-naive boys with dystrophinopathy. We evaluated 196 steroid-naive boys with dystrophinopathy who were enrolled in the Finding the Optimal Regimen for Duchenne Muscular Dystrophy trial. The neurodevelopmental concerns and psychosocial adjustment challenges were analyzed in relation to <i>DMD</i> mutation. A parent or legal guardian reported neurodevelopmental concerns in 4 domains (speech, learning and attentional difficulties, and autism spectrum disorder [ASD]) and completed the Personal Adjustment and Role Skills Scale to assess psychosocial adjustment. We also assessed whether boys of <i>DMD</i> carrier mothers were more vulnerable to speech delay and learning difficulties. We found that 39% of boys were reported to have speech delay with a mean age of speaking at 28 months (range 7-66 months). Learning difficulties were reported in 28% of participants. Inattentive-overactive and oppositional-defiant behavior was reported in 8% and 5% of participants, respectively. Psychosocial adjustment challenges were reported in 4% of participants. An ASD diagnosis was reported in 3 participants. Speech delay and learning difficulties were more common in boys with mutations downstream of <i>DMD</i> exon 45. Neurodevelopmental concerns were not associated with <i>DMD</i> deletion, duplication, or point mutation subtype. Boys of <i>DMD</i> carrier mothers did not have longer speech delay or more learning difficulties. Our data support evidence for a relationship between neurodevelopmental concerns and <i>DMD</i> mutation. A longitudinal assessment of developmental trajectory is necessary to evaluate how specific <i>DMD</i> mutations affect brain function.