P167 – 2623: The wide spectrum of neuropsychiatric profile in DMD in relation to underlying dystrophin gene mutations

• Published in: European journal of paediatric neurology Vol. 19; pp. S140 - S141
• Main Authors: Deconinck, N, Ricotti, V, Mandy, W, Scoto, M, Messina, S, Pane, M, Laforesta, S, Baijot, S, Vita, G, Mercuri, E, Skuse, D.H, Muntoni, F
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2015
• Subjects: Neurology; Pediatrics
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/S1090-3798(15)30480-3

Objective Duchenne muscular dystrophy (DMD) is associated with neurodevelopmental disorders. The aim of the study was to fully characterize the neuropsychiatric profile and to explore underlying genotype/phenotype associations with brainexpressed dystrophin isoforms. Methods 130 DMD boys (mean age = 9.5 years) in four European neuromuscular centres (i.e. London, Brussels, Rome and Messina) were included in the study and completed IQ assessment and a screening questionnaire. Of these, 87 underwent complete neurodevelopmental assessment with structured diagnostic interview and parent reported questionnaire. The results were correlated to the underlying dystrophin gene mutations and the deduced pattern of brain dystrophin isoform expression. Results The overall mean score on the screening neurodevelopmental questionnaire was significantly abnormal compared to the general paediatric population (p<0.001), Intelligence was overall below the population mean, with intellectual disability observed in 26.2% (n=35) of boys. Autistic spectrum disorder was reported in 20.7% (n=18), hyperactivity in 24.1% (n=21), inattention in in 43.7% (n=38) internalising and externalising problems 31.0% (n=27) and 17.2% (n=15) respectively. Neuropsychiatric disorders clustered together, with over 1/3 of boys with ≥ two disorders. There were no simple correlations of the different types of neuropsychiatrie disorders to mutation type but mutations affecting the 3' Dp140 and Dp71 isoforms showed a more dramatic neurocognitive profile. Conclusion Boys with DMD are at very high risk of neuropsychiatric disturbance, including clinically severe difficulties with intellectual development, social-communication, flexibility, anxiety, hyperactivity and attention. This risk increases with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which require prompt evaluation and early intervention. Our findings further emphasize the role that dystrophin plays in brain development and function.