Angelman syndrome: review of clinical and molecular aspects

Bird, Lynne M.

doi:10.2147/tacg.s57386

Cited by 179 publications

(169 citation statements)

References 142 publications

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“…VNS, if paired with the appropriate regimen of behavioral exposure or cognitive training, may represent a potential intervention to improve these disorders. Plasticity is a core deficit in many postnatal developmental disorders, including autism and forms of mental retardation [106][107][108][109]. Rehabilitative therapies do provide benefits in patients with postnatal developmental disorders.…”

Section: Potential Applications For Other Cognitive and Psychiatric Dmentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Section: Potential Applications For Other Cognitive and Psychiatric Dmentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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“…Movement disorders include tremors, jerkiness, and ataxia. The characteristic behaviors of AS include mouthing of objects, happy demeanor with easily provoked laughter, attraction to water, hyperactivity, short attention span, and decreased sleeping (see recent reviews for more detailed description of the clinical phenotype [2][3][4]). These features of AS can be seen in other neurodevelopmental disorders, leading to a broad differential diagnosis [5], which has recently been reviewed (Table 1) [6].…”

Section: Clinical Overviewmentioning

confidence: 99%

“…1) [7]. While there is variability with each molecular class of AS, in general those with deletion have a more severe phenotype, and those with UPD and imprinting defects a less severe phenotype [2,[8][9][10][11]. The diagnostic algorithm described in Fig.…”

Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

“…UBE3A sequencing that returns normal excludes point mutations, but small deletions within UBE3A require multiplex ligationdependent probe amplification for detection [13]. While it was formerly believed that 10-15 % of cases of AS were due to an as-yet-unrecognized molecular etiology, it is more likely that these patients represent phenocopies and actually have other diagnoses, such as those listed in Table 1 [2,6].…”

Section: Genetic Etiology and Diagnosismentioning

confidence: 99%

“…Treatment is supportive and includes 1) therapies to mitigate gross and fine motor delays; 2) augmentative communication strategies such as the use of communication devices, picture exchange cards, and modified sign language; and 3) intervention for comorbid ASD when present [2][3][4][8][9][10]. The remainder of treatment is limited to managing the problems associated with AS [66].…”

Section: Treatment Currentmentioning

confidence: 99%

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Angelman Syndrome

et al. 2015

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In this review we summarize the clinical and genetic aspects of Angelman syndrome (AS), its molecular and cellular underpinnings, and current treatment strategies. AS is a neurodevelopmental disorder characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. AS is caused by disruption of the maternally expressed and paternally imprinted UBE3A, which encodes an E3 ubiquitin ligase. Four mechanisms that render the maternally inherited UBE3A nonfunctional are recognized, the most common of which is deletion of the maternal chromosomal region 15q11-q13. Remarkably, duplication of the same chromosomal region is one of the few characterized persistent genetic abnormalities associated with autistic spectrum disorder, occurring in >1-2 % of all cases of autism spectrum disorder. While the overall morphology of the brain and connectivity of neural projections appear largely normal in AS mouse models, major functional defects are detected at the level of context-dependent learning, as well as impaired maturation of hippocampal and neocortical circuits. While these findings demonstrate a crucial role for ubiquitin protein ligase E3A in synaptic development, the mechanisms by which deficiency of ubiquitin protein ligase E3A leads to AS pathophysiology in humans remain poorly understood. However, recent efforts have shown promise in restoring functions disrupted in AS mice, renewing hope that an effective treatment strategy can be found.Key Words Angelman syndrome . neurodevelopmental disorders . autism . ubiquitin ligase . Ube3a . Imprinting. Clinical OverviewIn 1965, the English physician Harry Angelman described 3 patients who presented with a stiff, jerky gait, absence of speech, excessive laughter, and seizures. The disorder that came to bear his name [Angelman syndrome (AS)] is now recognized to affect approximately 1 in 15,000 individuals and is characterized by motor dysfunction, severe intellectual disability, speech impairment, seizures, hyperactivity, and autism spectrum disorder (ASD) as a common comorbidity [1].Developmental delay in individuals with AS is usually observed within the first year of life. Though most individuals lack speech entirely, some who are mildly affected can acquire a few words. Receptive language is less impaired. Seizures occur in >80 % of patients, and onset is usually before the age of 3 years. Movement disorders include tremors, jerkiness, and ataxia. The characteristic behaviors of AS include mouthing of objects, happy demeanor with easily provoked laughter, attraction to water, hyperactivity, short attention span, and decreased sleeping (see recent reviews for more detailed description of the clinical phenotype [2][3][4]). These features of AS can be seen in other neurodevelopmental disorders, leading to a broad differential diagnosis [5], which has recently been reviewed (Table 1) [6]. Overlapping clinical features may indicate common neurophysiological pathways,

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Autism Spectrum Disorders

Anderson

2018

Developmental Neuropathology

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Angelman syndrome: review of clinical and molecular aspects

Cited by 179 publications

References 142 publications

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Angelman Syndrome

Autism Spectrum Disorders

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