Duchenne muscular dystrophy and epilepsy

Pane, Marika; Messina, Sonia; Bruno, Claudio; D’Amico, Adele; Villanova, Marcello; Brancalion, B.; Sivo, Serena; Bianco, F.; Striano, Pasquale; Battaglia, Domenica; Lettori, Donatella; Vita, Gianluca; Bertini, Enrico; Gualandi, Francesca; Ricotti, Valeria; Ferlini, Alessandra; Mercuri, Eugenio

doi:10.1016/j.nmd.2013.01.011

Cited by 66 publications

(59 citation statements)

References 7 publications

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“…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%

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: 4mentioning

confidence: 99%

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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“…These data demonstrate that DG is regulated in a physiologically relevant manner in neurons and that DG and its glycosylation are essential for homeostatic plasticity at inhibitory synapses. muscular dystrophy | excitation-inhibition balance | dystrophin | AMPA receptors | retardation M uscular dystrophies are often associated with mild to severe cognitive deficits, epilepsy, and other neurological deficits (1)(2)(3). This is particularly evident in muscular dystrophies caused by mutations that affect glycosylation of the membrane glycoprotein α-dystroglycan (α-DG) (4).…”

mentioning

confidence: 99%

Dystroglycan mediates homeostatic synaptic plasticity at GABAergic synapses

Pribiag

Peng

Shah

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Dystroglycan (DG), a cell adhesion molecule well known to be essential for skeletal muscle integrity and formation of neuromuscular synapses, is also present at inhibitory synapses in the central nervous system. Mutations that affect DG function not only result in muscular dystrophies, but also in severe cognitive deficits and epilepsy. Here we demonstrate a role of DG during activitydependent homeostatic regulation of hippocampal inhibitory synapses. Prolonged elevation of neuronal activity up-regulates DG expression and glycosylation, and its localization to inhibitory synapses. Inhibition of protein synthesis prevents the activity-dependent increase in synaptic DG and GABA A receptors (GABA A Rs), as well as the homeostatic scaling up of GABAergic synaptic transmission. RNAi-mediated knockdown of DG blocks homeostatic scaling up of inhibitory synaptic strength, as does knockdown of like-acetylglucosaminyltransferase (LARGE)-a glycosyltransferase critical for DG function. In contrast, DG is not required for the bicuculline-induced scaling down of excitatory synaptic strength or the tetrodotoxin-induced scaling down of inhibitory synaptic strength. The DG ligand agrin increases GABAergic synaptic strength in a DG-dependent manner that mimics homeostatic scaling up induced by increased activity, indicating that activation of this pathway alone is sufficient to regulate GABA A R trafficking. These data demonstrate that DG is regulated in a physiologically relevant manner in neurons and that DG and its glycosylation are essential for homeostatic plasticity at inhibitory synapses. muscular dystrophy | excitation-inhibition balance | dystrophin |

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Duchenne muscular dystrophy and epilepsy

Cited by 66 publications

References 7 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

Dystroglycan mediates homeostatic synaptic plasticity at GABAergic synapses

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