G.P.175: Cognitive and neurobehavioral profile and its relation with genotype mutation in boys with Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular condition Mutations which affect the Dp71 and Dp140 dystrophin isoforms have been associated with intellectual disability (ID). There is only one report which evaluated a potential correlation between Attention deficit and Hyperactivity Disorders (ADHD) and the disruption of the Dp71 and Dp140 isoforms. In a study of 8 patients, disruption of the Dp140 isoform was associated with Autism Spectrum Disorder (ASD) in 5 patients. To describe the cognitive and neurobehavioral profile of boys with DMD at Holland Bloorview Kids Rehabilitation Hospital and its relation with the specific dystrophin isoforms affected. A retrospective chart review identified 201 patients with Dystrophinopathies seen over the past 10 years, 193 were identified to have DMD. Of those, 59 had neuropsychological testing (mean age 9.78 yrs). LD was found in 42%, ID in 20%, ADHD in 31%, ASD in 15%, anxiety in 26% and obsessive compulsive disorder (OCD) in 7%. Mutations affecting the Dp260 and Dp140 untranslated isoforms were seen in 15/25 (60%) with LD, 10/20 (50%) with ID, 7/9 (77%) with ASD, 15/16 (94%) with anxiety and 4/4 (100%) with OCD. Although the numbers of patients with mutations affecting Dp71 are small (3), 2/3 (66%) had ID. This is the first study to evaluate the association between isoform disruption and neurobehavioural comorbidities in patients with DMD. Further studies are needed to validate if there is an association and to understand the role of these isoforms in brain function.