Overview

The SeeSystem, as developed by GeneticaLens, facilitates the diagnosis and treatment of rare and difficult to diagnose disorders through a unique system of video documentation, integrated with a searchable system of metadata – to provide targeted searches and correct results quickly and efficiently, while accessing hundreds of hours of video

Angelman syndrome (AS) is a genetic disorder resulting in virtual lack of speech and severe intellectual disability. AS was first described by Harry Angelman in 1965. Since that time, researchers have established the genetic cause of AS, families have organized into a major organization, The Angelman Syndrome Foundation, and research is underway on possible targeted therapies. But there is a need for clear parameters and descriptions of clinical symptoms so that end points can be established not just for use in trials of possible targeted therapies, but also to provide objective measures of the effectiveness of palliative treatments and therapies.

The proposed SeeSystem-AS application will be supported by an extensive and scalable library of documentaries and video clips originally created as part of the Angelman Project between 1996 and 2002, funded by two National Institutes of Health (NIH) grants, This library contains video on 73+ individuals with AS, SeeSystem-AS will include the original videos (400+) created during the grant periods. Thirty-five DVDs were created at the time of the grant but only four were put into distribution. These four contained footage from of all subjects filmed, but many clips and documentaries providing additional detail on therapies, family life were not put into distribution as they were outside the scope of the grant at the time. SeeSystem-AS will contain the complete library of original documentaries and clips created for the Angelman Project.

In addition, GL proposes to follow up on individuals in this database (pending their availability) in order to document changes over time (as many as 15 years have passed for some of the Angelman Project’s original subjects.) The results of this follow-up will inform the creation of the development of a Quality of Life (QOL) measure for individuals with AS, which will be developed via interviews with family and clinicians familiar with the individual with AS.

Angelman syndrome (AS) is a rare disorder – people with AS are intellectually disabled, and have little if any expressive speech. Adults with AS are unable to live independently. Research is now in progress on possible targeted therapies for AS and there are numerous palliative therapies that are recommended for treatment of AS.

Individuals with AS cannot express their needs and wants and depend on caregivers to represent them to the myriad of clinicians and therapists involved in their care. In a sense, these family members and caregivers are informants – they are experts who can help develop and refine the clinical descriptions and features of AS because of their constant contact with these individuals. Their insights are a potentially valuable resource for researchers and others who need information on AS but do not have the opportunity to see individuals with AS on a regular basis. These interviews will be paired with footage of the behaviors described, key words will be added, and these clips will be used to establish QOL baselines for AS and help evaluate the success or failure of present and future options for intervention and treatment.

The Rare Diseases Clinical Research Network Angelman Syndrome Consortium (RDCRN-AS) consists of 6 study sites across the U.S. Since 2006 a total of around 270 children and adults with AS have been enrolled in the Natural History Study. Each year an updated medical history is obtained and a physical examination is performed. A licensed child psychologist performs a developmental assessment; a formal assessment of autism and an EEG is obtained every other year. The aim of the Natural History study is to help investigators learn more about the medical complications as well as the developmental and behavioral profile of individuals with Angelman syndrome across all age groups, with the long-term goal of being able to provide better care for these individuals and to develop effective treatments, which are presently limited to supportive (palliative) therapy.

Principal Investigator of the Natural History Study, Wen-Hann Tan, BMBS, explains:

• AS is caused by a deficiency of a maternally-expressed gene and is manifested at birth. Symptoms may include, but are not limited to, functionally severe developmental delay, speech impairments, movement or balance problems, and behavioral uniqueness, including a combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements and short attention span.
• We are conducting an observational study, following children with AS over 5 to 10 years to gain a better understanding of disease progression and the clinical features of AS's four molecular subclasses. The study will also attempt to establish genotype-phenotype correlations, which might aid in clinical care of AS patients.

The proposed project, SeeSystem-AS, will be developed by GeneticaLens in collaboration with the RDCRN-AS in order to facilitate the documentation process of the Natural History Study, by offering reference videos on AS, templates for data description and analysis developed by the previous Angelman Project research, videos and data from a new follow up study of the individuals who are part of the Angelman Project in order to document changes over time, and a new platform to help RDCRN-AS researchers upload and tag new video as they see and examine the Natural History study subjects year after year. The new platform, combined with on-going documentation of Natural History study subjects, will spur an expanding resource, bringing together subjects, families, and experts worldwide.

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