Research protocol: The initiation, design and establishment of the Global Angelman Syndrome Registry

Tones, Megan; Cross, Meagan; Simons, Chloe; Napier, Kathryn R.; Hunter, Adam; Bellgard, M.; Heussler, Honey

doi:10.1111/jir.12482

Cited by 19 publications

(34 citation statements)

References 32 publications

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“…Several biotechnology companies have received orphan drug designation of various products from the FDA and European Commission for faster development of commercially viable therapeutics. There has been significant progress in the establishment of a global patient registry to identify suitable patients for recruitments in the clinical trials [87,88]. However, proper cost-effective analysis is needed to balance the economic burden of the disease with these potential ultra-costly therapeutics.…”

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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“…[4][5][6] According to the definition presented by the National Committee on Vital and Health Statistics, a patient or a disease registry is an organized system for collection, storage, retrieval, analysis, and dissemination of information being widely applied in medicine and public health domain. 7,8 Registries are essential tools for providing information about the prevalence and natural history of a particular type of disease, discovering associated environmental and genetic factors, and prognosis related to different therapeutic approaches. [8][9][10][11] From administrative perspectives, patient and disease registries are efficient tools in improving health outcomes as well as reducing treatment costs.…”

Section: Introductionmentioning

confidence: 99%

The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study

et al. 2020

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Background: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report. Methods: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations. Results: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals. Conclusion: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease.

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“…1 The paucity of data can be attributed to a number of factors, including the absence of a newborn screening program for AS, overlapping phenotypic characteristics with other syndromes, issues pertaining to the accuracy of diagnostic methods, the lack of genetic confirmation for approximately 10% of cases, the establishment of a global registry only in 2016, and historically low levels of awareness among clinicians. 1,[5][6][7] The latter is driven by a number of factors, including that AS was only first described in 1965, the major genetic mechanism was not recognised until the 1980s, and consensus regarding the clinical diagnostic criteria was only achieved in 1995. 1,5,8 Many of these factors mean that children with AS, and their families, are often subject to a 'lengthy diagnostic odyssey' with most only receiving a diagnosis between the ages of one and five years.…”

Section: Introductionmentioning

confidence: 99%

Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years

Hartmanis¹,

Baker

Godler

et al. 2021

Preprint

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Purpose Angelman syndrome (AS) is a severe neurodevelopmental condition associated with a significant socioeconomic burden. However, no studies have thus far quantified or monetised the parental productivity burden of AS. The present study sought to estimate this burden. Methods The parental productivity burden of AS in Australia was estimated using cost-of-illness modelling with simulated follow-up over a 10-year period using 2019 as the baseline year. This involved estimating the prevalence of persons with AS and their parents, the productivity adjusted life years (PALYs) lost by parents, and the corresponding cost to society. Results The productivity burden borne by the estimated 153 to 1,322 (lower to upper scenario) parents of the 199 to 1,714 persons with AS ranged from 229.6 to 1,980.2 PALYs (discounted). This corresponded to a societal cost (discounted) of AUD$21.0 to $181.2 million, and a loss of 38% of PALYs per-parent. Conclusion AS imposes a significant productivity burden on Australian parents of affected persons, with a large associated impact on the broader economy. These findings are important for informing government planning regarding the supports that should be provided to persons with AS and their families. They will also be important for informing the reimbursement strategy for AS therapies.

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Research protocol: The initiation, design and establishment of the Global Angelman Syndrome Registry

Abstract: Findings indicate a need to consider recruitment strategies that target caregivers of older children and adults, and parents and caregivers from non-English speaking backgrounds.

Cited by 19 publications

References 32 publications

Epilepsy in Angelman syndrome: A scoping review

Epilepsy in Angelman syndrome: A scoping review

The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study

Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years

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