Seizure treatment in Angelman syndrome: A case series from the Angelman Syndrome Clinic at Massachusetts General Hospital

Shaaya, Elias; Grocott, Olivia; Laing, Olivia; Thibert, Ronald L.

doi:10.1016/j.yebeh.2016.04.030

Cited by 35 publications

(34 citation statements)

References 23 publications

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“…This is the largest clinical cohort described thus far. Our data confirm the distribution of the genetic subtypes, the overall clinical presentation and the presence of a more severe phenotype in the 15q11.2‐q13 deletion subtype (Clayton‐Smith & Laan, ; Luk & Lo, ; Mertz et al, ; Shaaya, Grocott, Laing, & Thibert, ; Tan et al, ). Novel findings are a negative association of epilepsy and an earlier age at onset of epilepsy on development, a high occurrence of NCSE, crouch gait in the older children, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia in all genetic subtypes.…”

Section: Discussionsupporting

confidence: 84%

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Heus

Mous

Hooven‐Radstaake

et al. 2019

American J of Med Genetics Pt A

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This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2-q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow-up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family. K E Y W O R D S development, epilepsy, genotype-phenotype, growth, UBE3A

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Section: Discussionsupporting

confidence: 84%

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Heus

Mous

Hooven‐Radstaake

et al. 2019

American J of Med Genetics Pt A

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“…One exception to this rule is seizures, which may be robustly and reliably induced in AS mouse models [23, 30]. However, the use of seizures as a biomarker in AS children is limited; seizures are typically treated with antiepileptic medications and are controlled to a great extent in the majority of children [36]. Delta rhythmicity represents a robust, reliable biomarker with strong face validity between mouse models and patient populations.…”

Section: Discussionmentioning

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

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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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“…For example, the 15q duplication cohort responded better than anticipated to drugs that are typically used for focal seizures, i.e., carbamazepine and oxcarbazepine, despite the fact that individuals with 15q duplications present with generalized epilepsy seizure types [8]. The DS, AS, and WHS also present with generalized epilepsy types, such as tonic-clonic, tonic, clonic, and myoclonic types, but in contrast to the 15q duplication syndrome cohort, individuals from all three of these groups responded better to broad spectrum drugs levetiracetam, clobazam, and lamotrigine [16,23]. Carbamazepine, oxcarbazepine, and phenytoin (the carboxamide group drugs) perform poorly for individuals with DS [16] and they also performed poorly for our WHS cohort.…”

Section: Other Studies That Correlate Genetic Etiology With Drug Respmentioning

confidence: 99%

A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf–Hirschhorn syndrome

Markham

Twede

et al. 2018

Epilepsy & Behavior

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Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a p<0.0001 after multiple comparison adjustment). This is the largest survey to date assessing WHS seizures. This study design is susceptible to possible bias, as the data are largely drawn from caregiver report and investigators had limited access to medical records. Despite this, our data suggest that the genetic etiology of seizures, together with an accurate electroclinical delineation, are important components of drug selection, even in contiguous gene syndromes which may have complex seizure etiologies.

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Seizure treatment in Angelman syndrome: A case series from the Angelman Syndrome Clinic at Massachusetts General Hospital

Cited by 35 publications

References 23 publications

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

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

A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf–Hirschhorn syndrome

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