Electroclinical characteristics of seizures—comparing Prader-Willi syndrome with Angelman syndrome

Wang, Pen-Jung; Hou, Jia‐Woei; Sue, Whey-Chen; Lee, Wang-Tso

doi:10.1016/j.braindev.2003.11.009

Cited by 29 publications

(36 citation statements)

References 24 publications

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“…Thus, spectral analyses are best suited for quantifying broad delta biomarkers. We chose to focus on delta rhythmicity because it is the most common EEG abnormality in AS and the most specific abnormality to AS relative to related disorders [20, 24]. However, interictal epileptiform discharges and theta abnormalities have also been widely reported [14, 17, 20, 21, 38].…”

Section: Discussionmentioning

confidence: 99%

“…We refined analysis methods during mouse studies and used these parameters for subsequent human EEG data analysis. We allowed for the possibility that mouse studies would shift our area of interest to other frequencies (e.g., theta) that have also been reported as abnormal in AS [14, 17, 20, 21, 24]; however, because mouse studies confirmed delta abnormalities with largely normal power in other frequency bands, we entered human studies with the original prespecified hypothesis that delta power is increased. We became interested in a secondary experimental question—the dynamics of delta abnormalities in AS—during mouse studies.…”

Section: Methodsmentioning

confidence: 99%

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Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Sidorov

Deck

Dolatshahi

et al. 2017

J Neurodevelop Disord

141

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BackgroundClinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical population or validated in a preclinical model. Here, we sought to quantitatively measure delta rhythmicity and evaluate its fidelity as a biomarker.MethodsWe quantified delta oscillations in mouse and human using parallel spectral analysis methods and measured regional, state-specific, and developmental changes in delta rhythms in a patient population.ResultsDelta power was broadly increased and more dynamic in both the Angelman syndrome mouse model, relative to wild-type littermates, and in children with Angelman syndrome, relative to age-matched neurotypical controls. Enhanced delta oscillations in children with Angelman syndrome were present during wakefulness and sleep, were generalized across the neocortex, and were more pronounced at earlier ages.ConclusionsDelta rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in both preclinical and clinical settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9195-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Sidorov

Deck

Dolatshahi

et al. 2017

J Neurodevelop Disord

141

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“…About 70% of PWS patients have a paternal deletion of the 15q11–q13 region, 25% of the remaining subjects have a maternal uniparental disomy (UPD), and 5% have an imprinting center defect [Goldstone et al, ]. Although 80% of patients with Angelman syndrome (results due to lack of expression of the maternally inherited UBE3A gene on chromosome 15q11–q13) experience epilepsy and difficulty in controlling their seizures [Wang et al, ], PWS has not been widely regarded as a disorder with a risk factor for seizures.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have noted a higher risk of seizures in patients with PWS than in the general population [Hall and Smith, ; Bray et al, ; Williams et al, ; Butler et al, ; Varela et al, ; Wang et al, ; Fan et al, ; Vendrame et al, ; Sinnema et al, ], and there was some correlation between the prevalence of seizures and PWS caused by deletions rather than by UPD [Fan et al, ; Vendrame et al, ]. Therefore, we retrospectively investigated the frequency and characteristics of seizures and examined genotype–phenotype correlations with respect to seizures in patients with PWS.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the frequency and characteristics of seizures in 142 Japanese patients with prader–willi syndrome

Takeshita

Murakami

Sakuta

et al. 2013

American J of Med Genetics Pt A

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Prader-Willi syndrome (PWS) has not been widely regarded as a disorder with a risk factor for seizures. We retrospectively investigated the frequency and characteristics of seizures and examined genotype-phenotype correlations with respect to seizures in PWS. We analyzed 142 patients with PWS and identified 31 (22%) with seizures. The most common seizure type was febrile convulsion (12%, 17/142). Epilepsy occurred in 6% of the patients in our cohort (9/142). The frequencies of febrile seizure and epilepsy in PWS were higher than those in the general population. Our study suggested that the frequency of seizures was not associated with genotypes of PWS (P = 0.35). In our study patients with PWS, 68% of the patients with seizures experienced initial episodes before they were 2 years old, and the seizures were relatively easier to manage.

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“…It has been suspected that sympathovagal imbalance in people with RTT may contribute to sudden cardiac death [23,46]. RTT patients often have recurrent seizures [47], and a similar situation may occur in patients with other neurogenetic disorders, such as fragile syndrome [48][49][50], Angelman syndrome [51][52][53] and Prader-Willi syndrome [54,55]. The authors hypothesized that nervous system abnormalities cause remodeling of the heart in RTT patients, including elevation of persistent sodium current, and suggested that sodium channel blockers, such as phenytoin, be tested as therapeutic agents.…”

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confidence: 99%

Rett Syndrome: Translate Medicine from Brain to Heart

Wang¹

2012

Brain Disord Ther

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Rett syndrome (RTT) is a X-linked neurodevelopmental disorder that affects approximately 1 in 10,000 live female births and is characterized by delayed-onset loss of spoken language, loss of hand use, problems with ambulation, and the development of distinctive hand stereotypes [1][2][3][4][5][6][7][8][9][10][11][12]. RTT is typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) [1,2,5,[8][9][10]13,14], a gene encoding a protein involved in regulation of gene expression [3,13,15,16]. In addition to the cognitive and motor abnormalities, RTT patients also show autonomic dysfunction, with breathing and heart rate irregularities [17][18][19][20]. Boys with mutations in MECP2 show more severe autonomic dysfunction, with marked breathing and heart rate abnormalities that usually result in death within the first year of life [21]. RTT patients have a high incidence of sudden unexpected deaths (26% of all deaths) [22], which are probably of cardiac origin. Previous studies have shown that some RTT patients have prolonged QT intervals (LQT) on electrocardiograms (ECGs) [23]. In patients with other diseases, LQT is a significant risk factor for sudden arrhythmic cardiac death [24]. However, so far the causes for LQT in RTT and its contribution to the high proportion of sudden death are still unknown. As reported recently in Science Translational Medicine, McCauley et al. [25] tested the hypothesis that these sudden deaths in RTT patients may be due to cardiac dysfunction.In most cases, inherited LQT are caused by mutations in the voltage-gated potassium channels KVLQT1 (LQT1) and HERG (LQT2) and in the voltage-gated sodium channel SCN5A (LQT3) [26][27][28][29]. Rare mutations in genes encoding other channel subunits and other cardiac proteins such as caveolin-3 [30], may also contribute to some cases of inherited LQT. Since RTT patients have MeCP2 dysfunction, which causes the LQT phenotype, McCauley et al. [25] aimed at understanding whether (I) MeCP2 dysfunction in mice can recapitulate the long QT phenotype and cause predisposition to arrhythmic-induced death after programmed electrical stimulation (PES); (II) neuronal tissue specific MeCP2 dysfunction is sufficient to reproduce the LQT phenotype; and (III) alterations in the sodium current contribute to the LQT phenotype in this mouse model of RTT.Firstly, McCauley et al. [25] examined ECGs in 379 female patients with typical RTT to define the prevalence of electrophysiological abnormalities in RTT. The authors found that 18.5% of these patients had long corrected QT interval (QTc), consistent with previous reports [23,31,32]. They thought that these 18.5% of affected individuals are likely at risk for sudden death since 26% of deaths in RTT are sudden and unexpected [24]. The authors then tried to identify electrophysiological abnormalities in mouse models of RTT. They found that hemizygous male Mecp2Null/Y mice have severe early-onset LQT and QRS prolongation, and heterozygous female Mecp2 Null /+ show prolongation of both parameters that becomes...

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Electroclinical characteristics of seizures—comparing Prader-Willi syndrome with Angelman syndrome

Cited by 29 publications

References 24 publications

Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Evaluating the frequency and characteristics of seizures in 142 Japanese patients with prader–willi syndrome

Rett Syndrome: Translate Medicine from Brain to Heart

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