Epilepsy and sleep disorders improve in adolescents and adults with Angelman syndrome: A multicenter study on 46 patients

Sueri, Chiara; Ferlazzo, Edoardo; Elia, Maurizio; Bonanni, Paolo; Randazzo, Giovanna; Gasparini, Sara; D’Agostino, Tiziana; Sapone, Antonino R.; Ascoli, Michele; Bellavia, Marina; Cianci, Vittoria; Gambardella, Antonio; Labate, Angelo; Aguglia, Umberto

doi:10.1016/j.yebeh.2017.07.041

Cited by 22 publications

(15 citation statements)

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“…Several studies in AS reported severe seizures in early childhood with a distinct improvement during later childhood [61][62][63]. Seizure remission in late teens and early twenties followed by recurrence of seizures in third or fourth decades has been reported [64].…”

Section: Discussionmentioning

confidence: 99%

Epilepsy in Angelman syndrome: A scoping review

Samanta

2021

Brain and Development

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Angelman Syndrome (AS) is characterized by severe developmental delays including marked speech impairment, movement abnormalities(ataxia, tremor), and unique behaviors such as frequent laughter and is caused by dysfunctional maternal UBE3A gene (maternal 15q11-13 deletions, maternal specific UBE3A mutation, uniparental disomy, and imprinting defect). Intractable epileptic seizures since early childhood with characteristic EEG abnormalities are present in 80-90% patients with AS. Underlying pathophysiology may involve neocortical and thalamocortical hyperexcitability secondary to severe reduction of GABAergic input, as well as dysfunctional synaptic plasticity, deficient synaptogenesis, and neuronal morphological immaturity. The onset of epilepsy is most prevalent between 1 and 3 years of age; however, approximately 25% of patients developed epilepsy before one year of age. Various types of generalized seizures are most prevalent, with most common types are myoclonic and atypical absence. More than 95% of epilepsy patients may have daily seizures at least for a limited time during early childhood, and two-third patients develop disabling seizures. Fever provoked seizures, and frequent occurrence of nonconvulsive status epilepticus are two unique features. Seizures are frequently pharmacoresistant. Considering underlying prominent GABAergic dysfunction, clinicians had used AEDs that target GABAergic signaling such as valproate, phenobarbital, and clonazepam as first-line therapies for AS. However, due to the unfavorable side effect profile of these AEDs, a recent treatment approach involves priority use of levetiracetam, clobazam, topiramate, lamotrigine, ethosuximide, VNS, and carbohydrate-restricted diets. Besides symptomatic management, there has been recent progress to find a curative treatment with the following approaches: 1. Gene/protein replacement therapy (Adeno and lentiviral vector therapy to deliver a gene or secretory protein); 2. Activation of the intact but silent paternal copy of UBE3A (antisense oligonucleotide therapy and artificial transcription factors); and 3. Downstream therapies (OV101/gaboxadol, ketone supplement, novel compounds/peptides, anti-inflammatory/regenerative therapy).

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Section: Discussionmentioning

confidence: 99%

Epilepsy in Angelman syndrome: A scoping review

Samanta

2021

Brain and Development

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“…Seizures are common in AS, with multiple studies supporting that over 80% of AS patients have epilepsy, with nearly one in four having seizures in the first year of life (Sueri et al, ; Williams et al, ). Consistent with this, over 80% of patients have epileptiform discharges on EEG or a stereotypical delta frequency activity.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this, over 80% of patients have epileptiform discharges on EEG or a stereotypical delta frequency activity. Though seizure frequency decreases over time, the typical EEG pattern persists (Sueri et al, ; Vendrame et al, ). In contrast with these findings, seizures were rare in our mAS cohort, though over 50% of mAS patients demonstrated EEG findings consistent with AS.…”

Section: Discussionmentioning

confidence: 99%

Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome

Carson

Bird

Childers

et al. 2019

Molec Gen & Gen Med

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Background Angelman Syndrome (AS) is a neurodevelopmental disorder with core features of intellectual disability, speech impairment, movement disorders, and a unique behavioral profile. Typically, AS results from absent maternal expression of UBE3A, but some individuals have imprinting defects in a portion of their cells. These individuals are mosaic for normal and defective UBE3A expression, resulting in mosaic AS (mAS) with a partial loss of gene expression. Methods This study aims to contrast the mAS phenotype to that of AS. Clinical characteristics of mAS were obtained from a parental survey of 22 mAS patients and from the Angelman Natural History study. These were contrasted with those of AS using historical data. Results Developmental delay was present in nearly all mAS patients, whereas the core features of AS were reported in less than 40%. While language and ability to manage activities of daily living were markedly improved over that expected in AS, mAS patients demonstrated a high incidence of behavioral challenges. Conclusion Clinical work‐up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader‐Willi such as hyperphagia.

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“…Epilepsy, which is a major clinical problem in many individuals with AS, can also affect both brain development and daily life functioning. The onset of epilepsy typically occurs in early childhood, although severity often improves with puberty (Thibert et al 2013;Sueri et al 2017). The concept of 'epileptic encephalopathy' embodies the notion that epileptic activity may alter synaptic plasticity and exacerbate cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone (Berg 2011;Brooks-Kayal 2011;Jeste & Tuchman 2015).…”

Section: Introductionmentioning

confidence: 99%

Hyperactive behaviour in Angelman syndrome: the association with sleep problems and age of epilepsy onset

Bakke

Howlin

Helverschou

2021

J intellect Disabil Res

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Background Sleep problems are common in many neurodevelopmental disorders, but little is known about how sleep is related to behavioural symptoms in Angelman syndrome (AS) or other genetic disorders. Hyperactive behaviour, sleep problems and epilepsy seem to be more common in AS than in other genetic conditions associated with severe intellectual disability. We hypothesised that both more sleep problems and earlier onset of epileptic seizures would predict more symptoms of hyperactivity. Hence, the aim of the project was to explore the association between hyperactive behaviour, sleep problems and age of epilepsy onset in individuals with AS. Method All known parents/guardians (n = 115) of individuals with AS in Norway were invited to participate in this descriptive correlational study. Fifty-six individuals (49%) responded, and 42 people (25 male and 17 female; mean age 18.5 years, range 2-57 years) with genetically verified AS were included. Scores for 'hyperactivity' and 'sleep problems' were derived from questionnaire data. Information on epilepsy was obtained from medical records. Results 'Hyperactivity' was positively correlated with 'total sleep problems' (r = 0.46, P = 0.002) and negatively correlated with 'age of epilepsy onset' (r = À0.47, P = 0.01). 'Age of epilepsy onset' was not correlated with 'total sleep problems'. An overall multiple regression model with 'hyperactivity' as the dependent variable and 'age of epilepsy onset' and 'total sleep problems' as covariates was significant (R 2 = 0.39, F = 8.16, P = 0.002). Hence, hyperactivity in AS could be predicted from both age of epilepsy onset and current sleep problems. Conclusions Sleep problems may increase hyperactivity symptoms in individuals with AS. The association between hyperactivity and sleep problems in AS indicates that both should be investigated together as part of routine clinical assessment and intervention for either area of difficulty. Younger age of epilepsy onset was associated with more hyperactivity in AS, which may be related to encephalopathic effects of seizures and epilepsy.

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Epilepsy and sleep disorders improve in adolescents and adults with Angelman syndrome: A multicenter study on 46 patients

Cited by 22 publications

References 15 publications

Epilepsy in Angelman syndrome: A scoping review

Epilepsy in Angelman syndrome: A scoping review

Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome

Hyperactive behaviour in Angelman syndrome: the association with sleep problems and age of epilepsy onset

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