Analysis of EEG patterns and genotypes in patients with Angelman syndrome

Vendrame, Martina; Loddenkemper, Tobias; Żarowski, Marcin; Gregas, Matt; Shuhaiber, Hans; Sarco, Dean; Morales, Augusto; Nespeca, Mark; Sharpe, Cia; Haas, Kevin F.; Barnes, Gregory; Glaze, Daniel G.; Kothare, Sanjeev V.

doi:10.1016/j.yebeh.2011.11.027

Cited by 63 publications

(71 citation statements)

References 19 publications

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“…Seizures have been reported in 90% of children with AS that have a 15q11 deletion and greater than 50% of children that have mutations specifically within the UBE3A gene (2,23,41). In all cases, the EEGs of individuals with AS have been found to be abnormal (42). Although EEGs are not necessarily identical between different people, a hallmark of the EEG defect in humans with AS is the occurrence of abnormal bouts of high amplitude and low frequency (2-3 Hz) δ-waves early in life.…”

Section: Discussionmentioning

confidence: 99%

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Mandel‐Brehm

Salogiannis

Dhamne

et al. 2015

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

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Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of-function mutations in the maternally inherited copy of the UBE3A gene, and is characterized by an absence of speech, excessive laughter, cognitive delay, motor deficits, and seizures. Despite the fact that the symptoms of AS occur in early childhood, behavioral characterization of AS mouse models has focused primarily on adult phenotypes. In this report we describe juvenile behaviors in AS mice that are strain-independent and clinically relevant. We find that young AS mice, compared with their wild-type littermates, produce an increased number of ultrasonic vocalizations. In addition, young AS mice have defects in motor coordination, as well as abnormal brain activity that results in an enhanced seizure-like response to an audiogenic challenge. The enhanced seizure-like activity, but not the increased ultrasonic vocalizations or motor deficits, is rescued in juvenile AS mice by genetically reducing the expression level of the activity-regulated cytoskeleton-associated protein, Arc. These findings suggest that therapeutic interventions that reduce the level of Arc expression have the potential to reverse the seizures associated with AS. In addition, the identification of aberrant behaviors in young AS mice may provide clues regarding the neural circuit defects that occur in AS and ultimately allow new approaches for treating this disorder.Angelman syndrome | ARC | EPHEXIN5 | ultrasonic vocalizations | EEG

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Section: Discussionmentioning

confidence: 99%

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Mandel‐Brehm

Salogiannis

Dhamne

et al. 2015

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

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“…The seizure activity can, however, be attenuated in adolescents (Thibert et al, 2009(Thibert et al, , 2013. The EEG of Patients with AS presents a very characteristic pattern (slow background activity mixed with spikes) (Vendrame et al, 2012), which can sometimes be useful in the diagnosis of AS. In fact, a previous report by Park et al (2012) characterized the EEG pattern in 86% of all Patients with AS as follows: a typical AS pattern characterized by runs of high-amplitude slow waves that were more prominent in the frontal region, mixed with spike and slow wave multifocal activity.…”

Section: Discussionmentioning

confidence: 99%

Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype

Wang

Hou

2016

Genet. Mol. Res.

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ABSTRACT. Angelman syndrome (AS) is a neurogenetic disorder caused by a defect in the expression of the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene in chromosome 15. The most common genetic defects include maternal deletions in chromosome 15q11-13; however, paternal uniparental disomy and imprinting defects allow for the identification of mutations in UBE3A in 10% of patients with AS. The aim of this study was to validate the clinical features and genetic polymorphisms of AS, and to discuss the relationship between functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas. Six children with AS (mean age = 32.57 months) presenting characteristic behavioral patterns of AS (frequent laughter and happy demeanor, hand flapping, and hypermotor behavior) were recruited to this study. The patients underwent a clinical evaluation (clinical history, dysmorphological and neurological examinations, and psychological evaluations) and paraclinical investigations [genetic tests (fluorescence in situ hybridization and methylation polymerase chain We conclude that AS diagnosis cannot rely solely on genetic testing for polymorphisms in UBE3A and must consider its clinical characteristics. Moreover, functional language lateralization and the arcuate fasciculus in the Broca's and Wernicke's areas were found to be closely correlated. Therefore, UBE3A gene mutation analysis combined with comprehensive clinical evaluations may be suitable for the diagnosis of AS.

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“…The most common EEG abnormality in AS concerns intermittent rhythmic (4-6 Hz), high-amplitude (>200 μvolts) theta waves (44%) and slow posterior activity (44%) [19]. Posterior sharp waves easily triggered by passive eye closure correlate with clinically severe epileptic seizures [19,20] and can be mixed with epileptic discharges [17,21]. Spikes tend to move from the posterior to the anterior regions of the brain over time [21], as observed in the six cases presented here.…”

Section: Discussionmentioning

confidence: 99%

“…Spikes tend to move from the posterior to the anterior regions of the brain over time [21], as observed in the six cases presented here. Finally, these EEG patterns are observed across all genotypes [19]. They may precede the diagnosis [17,19] but are not absolutely specific [3,7,22].…”

Section: Discussionmentioning

confidence: 99%

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Angelman Syndrome: A Case Series Assessing Neurological Issues in Adulthood

et al. 2014

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Background: This study aimed to evaluate the clinical symptoms of Angelman syndrome (AS) in adults and to identify the neurological pathways affected in this disease. AS is a neurogenetic disorder resulting due to the deletion or inactivation of the ubiquitin-protein-ligase E3A gene on maternal chromosome 15. Summary: A retrospective analysis of data from six adults patients with clinical, electroencephalographic and genetic confirmation of AS was performed. Movement disorders of the hands and mouth, laughing spells, severe expressive speech disorders, a happy nature, hyposomnia and anxiety are the major neurological characteristics of AS in adulthood. Cerebellar ataxia, muscle hypotonia and tremor, though constant in childhood, tend to be attenuated in adulthood. Epilepsy, one of the most frequent symptoms in childhood and in adulthood, is characterised by specific electroencephalographic patterns. Key Messages: These clinical characteristics are important to improve the clinical awareness and genetic diagnosis of AS. Clinicians must be better informed concerning the adult phenotype as it is not well described in the literature. We stress the importance of AS as one of the main causes of intractable epilepsy. The authors suggest frontal and cerebellar dysfunction. Further functional cerebral imaging studies are necessary.

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Analysis of EEG patterns and genotypes in patients with Angelman syndrome

Cited by 63 publications

References 19 publications

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression

Applicability of genetic polymorphism analysis for the diagnosis of Angelman syndrome and the correlation between language difficulties and disease phenotype

Angelman Syndrome: A Case Series Assessing Neurological Issues in Adulthood

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