The protocol used by Australian researchers to create the Global Angelman Syndrome Registry, the first worldwide patient registry dedicated to Angelman syndrome (AS), has been published. Preliminary results are included in the study, providing a characterization of the more than 450 people taking part so far.
More work is underway to encourage greater numbers of patients — and one representative of all patient ages and countries — to participate in order to best ensure that data collected benefits future research.
The study, “Research protocol: The initiation, design and establishment of the Global Angelman Syndrome Registry,” was published in the Journal of Intellectual Disability Research.
Researchers believe the registry will contribute to a better understanding of this disease’s natural history and be of unprecedented benefit to research into potential therapies and Angleman biomarkers.
Much of what is known about how Angelman syndrome affects patients has been obtained from case reports and small questionnaire studies. Preliminary results from the Angelman Syndrome Natural History Study (NCT00296764), a large research project that followed patients annually for at least five years, and up to more than 10 years, have challenged earlier findings and thinking about the natural history of Angelman.
This study identified a possible association between specific mutations and symptom severity in 92 Angelman children ages 5 or younger: those with a deletion in chromosome 15 showed more severe clinical and developmental symptoms than children with UBE3A mutations.
Still, efforts toward a fuller understanding of disease management and treatment are hampered by challenges that range from study groups too small to ensure accurate data — Angelman is a rare disease — to a limited understanding of its natural history, or its progression over time in the absence of treatment.
The Global Angelman Syndrome Registry, an initiative launched in 2016, is a worldwide online registry of Angelman patients driven by parents and families.
The registry is expected to help clinicians and researchers learn more about individuals with this syndrome, facilitate research and enable clinical trial sponsors to identify suitable patients for each study.
Started by the Foundation for Angelman Syndrome Therapeutics (FAST) Australia, the registry now spans contributions from stakeholders that include parents and families of patients, researchers and clinicians in the field, and pharmaceutical companies.
Entry to the registry is done directly by parents and caregivers of Angelman patients using the Angelman Syndrome Registry website.
They are asked to provide information about a patient’s clinical, behavioral and developmental status.
The registry consists of 10 modules covering demographics; developmental, diagnostic, medical and surgical history; behavior and development; epilepsy; medications; interventions; and sleep patterns. To create a longitudinal dataset, information on a given patient will be collected every year.
In the first year after its launch, 467 parents and caregivers had registered a child or adult patient.
To date, 59 percent of all those registered reside in North and South America, 23 percent in Europe, 17 percent in the Asia Pacific region, and 1 percent in the Middle East or Africa.
Most are children; 16 percent of those in the registry are age 20 or older.
Most participants — 76% — carry a chromosome deletion, while another 20% have a mutation, uniparental disomy — where 2 copies of a chromosome come from the same parent, rather than 1 copy from each parent — or an imprinting defect.
Recruitment is ongoing, and researchers are actively looking to encourage greater participation and improve data collection: the team wants the widest participation possible worldwide to prevent skews in data collected (currently, a high proportion of young patients are from English speaking countries), and to encourage older Angleman patients to join.
“An ethical amendment has been sought to widen recruitment strategies both online and offline to encourage the recruitment of older individuals with AS who may no longer live with their families or reach families who do not engage with online support groups,” the research team wrote.
To monitor potential bias, demographics of a registry sample will continue to be compared with those of other Angleman studies.
Researchers will also include available translated versions of the registry in Chinese, Spanish, French and Italian.