Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations
2015/09/14 by Valeria Ricotti, William Mandy, William P L Mandy +8 · 32 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Muscle Physiology and Disorders #Neurogenetic and Muscular Disorders Research #Genetic Neurodegenerative Diseases
paper · doi:10.1111/dmcn.12922
Abstract
AIM: 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. METHOD: 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. INTERPRETATION: 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.
Citations
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- Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy. [europepmc]
- Current Perspectives in Autism Spectrum Disorder: From Genes to Therapy. [europepmc]
- Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy. [europepmc]
- Myelination is delayed during postnatal brain development in the mdx mouse model of Duchenne muscular dystrophy. [europepmc]
- Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. [europepmc]
- Descriptive Phenotype of Obsessive Compulsive Symptoms in Males With Duchenne Muscular Dystrophy. [europepmc]
- Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy. [europepmc]
- Advances in imaging of brain abnormalities in neuromuscular disease. [europepmc]
- Dystrophin deficiency leads to dysfunctional glutamate clearance in iPSC derived astrocytes. [europepmc]
- Relationships between DMD mutations and neurodevelopment in dystrophinopathy. [europepmc]
- Dystrophin Dp71 and the Neuropathophysiology of Duchenne Muscular Dystrophy. [europepmc]
- Characterization of brain dystrophins absence and impact in dystrophin-deficient Dmdmdx rat model. [europepmc]
- Cognitive impairment appears progressive in the mdx mouse. [europepmc]
- Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy. [europepmc]
- Causes of clinical variability in Duchenne and Becker muscular dystrophies and implications for exon skipping therapies. [europepmc]
- Duchenne muscular dystrophy. [europepmc]
- Innovative Therapeutic Approaches for Duchenne Muscular Dystrophy. [europepmc]
- Associations between coronary heart disease and risk of cognitive impairment: A meta-analysis. [europepmc]
- Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. [europepmc]
- Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy. [europepmc]
- Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy. [europepmc]
- Neuromuscular Development and Disease: Learning From in vitro and in vivo Models. [europepmc]
- Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Duchenne Muscular Dystrophy: The Issue of Transgene Persistence. [europepmc]
- Tissue- and cell-specific whole-transcriptome meta-analysis from brain and retina reveals differential expression of dystrophin complexes and new dystrophin spliced isoforms. [europepmc]
- Duchenne muscular dystrophy: recent insights in brain related comorbidities. [europepmc]
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