title: Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.
abstract: OBJECTIVE
  Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations.
  
  
  METHODS
  One hundred and thirty males with DMD (mean age 9y 10mo, range 5-17y) in four European centres were included and completed IQ assessment and a neurodevelopmental-screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent-reported questionnaires.
  
  
  RESULTS
  The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3' end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms.
  
  
  CONCLUSIONS
  Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention.
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ricotti
authors.affiliation: Behavioural and Brain Sciences Unit, UCL Institute of Child Health, London, UK.
authors.forename: William P L
authors.initials: WP
authors.lastname: Mandy
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Scoto
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Pane
authors.affiliation: Department of Paediatric Neurology, NMRC, Universitair Ziekenhuis Gent, Gent, Belgium.|Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Universite Libre de Bruxelles, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deconinck
authors.affiliation: Department of Neurosciences and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Messina
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.|Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.affiliation: Behavioural and Brain Sciences Unit, UCL Institute of Child Health, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Skuse
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D000067877:Autism Spectrum Disorder / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D000066553:Problem Behavior
chemical_list: C484258:DMD protein, human; D016189:Dystrophin