Neurodevelopmental, behavioral, and emotional symptoms common in Duchenne muscular dystrophy

Abstract

Introduction We studied neurodevelopmental and behavioral/emotional symptoms in patients with Duchenne muscular dystrophy (DMD). Methods Retrospective case series of neurodevelopmental and behavioral/emotional symptoms obtained through review of systems of 700 DMD patients in relation to dystrophin gene mutations. Results The most common symptoms encountered were emotional/behavioral dysregulation (38.7%), inattention/hyperactive features (31.4%), obsessive and compulsive features (25.0%), and language/speech delays (24.4%). Most patients (72.7%) had at least one symptom. Patients with mutations near the 3′ end of the dystrophin gene were at higher risk for developing inattention/hyperactive features, language/speech delays, and global intellectual delays. Those with mutations between exon 31 and 79 had higher risk of clustering of symptoms when compared with those upstream of exon 30. Discussion Neurodevelopmental, emotional, and behavioral symptoms are common comorbidities in DMD. There is higher prevalence of inattention/hyperactive features, language/speech delays, and global intellectual delays in genotypes affecting the 3′ end of the dystrophin gene.

Startle responses in Duchenne muscular dystrophy: a novel biomarker of brain dystrophin deficiency

“…In the whole cohort there were weak-moderate significant correlations (rho=0.3-0.4) between IQ and all neuropsychiatric symptom scores apart from hyperactivity (Supplemental Table 2), but not in the separate DMD and Control groups, apart from a significant negative correlation of inattention with IQ in the DMD group. These data confirmed the divergence of the DMD participants from the Control group and normal population, in line with work from our group and others, [10][11][12] with particular emphasis on the more pronounced cognitive and neuropsychiatric problems in the DMD subgroup lacking the Dp140 isoform.…”

“…In recent years there has been an increasing understanding of the role that the multiple dystrophin isoforms have in brain function, both in human and various animal models. 10,11,[52][53][54] However, some aspects of the complex neurobehavioural phenotype are only now beginning to be better understood. There is growing evidence to suggest that dystrophin is implicated in fear and stress responses in experimental and naturally occurring animal models, including the exaggerated startle response in the mdx mouse, 18 but until now there has been no systematic study of equivalent responses in humans with DMD.…”

“…[7][8][9] There is evidence that suggests there is also an increased risk of emotional, behavioural and neurodevelopmental disorders in individuals lacking the shorter dystrophin isoforms, but this is not confirmed. [10][11][12] The heterogeneity of the neuropsychiatric presentation amongst individuals with DMD and the difference in phenotype in patients lacking different isoforms suggests that several pathophysiological mechanisms may be implicated in the different CNS phenotypes in DMD.…”

“…Anxiety disorders are associated with increased startle responses, 26 and anxiety symptoms are reported in 24-33% of people with DMD 11,27,28 although this is a much less well-characterised feature than other CNS aspects of DMD.…”

A scalable, clinically severe pig model for Duchenne muscular dystrophy

“…In addition to heart failure and progressive muscle weakness, many patients with DMD have cognitive and/or behavioral problems, which have great impact on the quality of life of both patients and their families (reviewed in (34)). To evaluate if DMD Y/pigs resemble also these aspects of human DMD, we performed two behavioral tests which both revealed significant differences from WT.…”