Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy

Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

doi:10.1177/0883073815570154

Cited by 162 publications

(202 citation statements)

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“…Our results rather emphasize the amygdala, involved in emotion regulation, and the hippocampus, involved in memory, based on their high expression of DMD and the supporting evidence of memory and emotion deficits in DMD from animal and neuropsychological studies in humans 5,26,48,49 . Moreover, we show a relatively even distribution of DMD expression throughout the cortex, involved in higher-order cognitive functioning.…”

Section: Discussionmentioning

confidence: 45%

“…Moreover, patients lacking Dp140 isoforms performed worse on all neuropsychological tests (general cognitive abilities, verbal memory, attention and executive functions) compared to those with preserved Dp140 25 . The relationship between the isoforms that are affected and the cognitive profile is further supported by the higher incidence of neurodevelopmental disorders in patients missing Dp140 compared to patients missing only Dp427 5,26 . This group distinction was already detectable below the age of four, as assessed with developmental quotients 8 .…”

Section: 4mentioning

confidence: 95%

“…Moreover, there is a higher incidence of attention-deficit/ hyperactivity disorder (ADHD) (32%), anxiety disorder (27%), autism spectrum disorders (ASD) (15%), epilepsy (6.3%), and obsessive-compulsive disorder (OCD) (4.8%) in patients with DMD [5][6][7] . The progressive nature of the muscle pathology is a hallmark of the disease.…”

Section: 4mentioning

confidence: 99%

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Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Doorenweerd

Mahfouz

Putten

et al. 2017

Neuromuscular Disorders

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Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked genetic neuromuscular disorders characterized by severe and progressive muscle weakness. Mutations in the DMD gene result in absent/non-functional muscle dystrophin protein in DMD and shortened/partially functional protein in BMD.In addition to skeletal muscle pathology, DMD is characterized by cognitive and behavioural problems with 30% of boys with DMD showing cognitive impairment (IQ < 70) 1 and 40% having reading deficits similar to those observed in patients with phonological dyslexia 2-4 . Moreover, there is a higher incidence of attention-deficit/ hyperactivity disorder (ADHD) (32%), anxiety disorder (27%), autism spectrum disorders (ASD) (15%), epilepsy (6.3%), and obsessive-compulsive disorder (OCD) (4.8%) in patients with DMD [5][6][7] . The progressive nature of the

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Section: Discussionmentioning

confidence: 45%

Section: 4mentioning

confidence: 95%

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Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Doorenweerd

Mahfouz

Putten

et al. 2017

Neuromuscular Disorders

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“…The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities that vary from mild learning disabilities to severe intellectual impairment, ASD, and behavioral disturbances. Seizures occur significantly more often in ASD þ Down than in Down only control (Molloy et al 2009) Dravet syndrome 24.3% 61.5% (Berkvens et al 2015) 100% (Wolff et al 2006) 100% (Berkvens et al 2015) Duchenne muscular dystrophy 15% (Banihani et al 2015) 6.3% (Pane et al 2013) Fragile X syndrome 21% (Kohane et al 2012) 30% ( The majority of individuals with TSCs have mutations of Tsc1 (encoding for the protein hamartin) or Tsc2 (encoding for the protein tuberin). Hamartin and tuberin proteins form a functional complex, which inhibits the serine/ threonine protein kinase mammalian target of rapamycin (mTOR) (Curatolo et al 2015).…”

Section: Genetics Of Epilepsy and Autismmentioning

confidence: 99%

Epilepsy and Autism

Buckley

Holmes

2016

Cold Spring Harb Perspect Med

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Epilepsy and autistic spectrum disorder frequently coexist in the same individual. Electroencephalogram (EEG) epileptiform activity is also present at a substantially higher rate in children with autism than normally developing children. As with epilepsy, there are a multitude of genetic and environmental factors that can result in autistic spectrum disorder. There is growing consensus from both animal and clinical studies that autism is a disorder of aberrant connectivity. As measured with functional magnetic resonance imaging (MRI) and EEG, the brain in autistic spectrum disorder may be under-or overconnected or have a mixture of over-and underconnectivity. In the case of comorbid epilepsy and autism, an imbalance of the excitatory/inhibitory (E/I) ratio in selected regions of the brain may drive overconnectivity. Understanding the mechanism by which altered connectivity in individuals with comorbid epilepsy and autistic spectrum disorder results in the behaviors specific to the autistic spectrum disorder remains a challenge.

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“…DMD occurs in early childhood, resulting in difficulties in physical exercise [2]. In addition, patients with DMD have a high rate of cognitive impairment and learning disabilities, which are related to the disruption of dystrophin isoforms in the central nervous system [7]. In BMD, muscle wasting and weakness are also noted as in DMD, but BMD is a milder form with a later onset, and patients have a much longer survival in comparison to DMD.…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

Kim

Seo

et al. 2017

J Genet Med

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JGMand may have near normal lives [2,3].The differential diagnosis of BMD and DMD in suspected cases is based on their clinical findings, muscle biopsy, and the mutations in DMD. Among these, positive staining for dystrophin in muscle biopsies is an important finding in the differential diagnosis [4,5]. However, since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutations in DMD gene identified in the patient. According to the mutation database or previous reports, each DMD mutation is classified as either a DMD-or BMDcausing mutation [6]. However, when a novel DMD mutation is identified, the differential diagnosis should be based on the muscle biopsy findings along with other clinical findings. IntroductionDuchenne and Becker muscular dystrophies (DMD, OMIM #310200 and BMD, OMIM #300376; respectively) are caused by mutations in DMD, the dystrophin-coding gene. These conditions are inherited in an X-linked recessive manner with a prevalence of 1 in 4,000 to 5,000 new born males [1].DMD and BMD are characterized by progressive muscular weakness. DMD is a severely disabling neuromuscular disease that leads to premature death of patients at approximately 19 years of age due to cardiac or respiratory failure. In contrast, BMD is a milder form with a later onset and slower rate of progression, and patients older than 16 years remain ambulatory www.e-kjgm.org Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.

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Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy

Cited by 162 publications

References 81 publications

Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Epilepsy and Autism

Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

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