Title: “We know so much so use us!!” - Improving the treatment for children with GENetic Rare disease: Observational Cohort study (GenROC)
Funder: Department of Health and Social Care

Abstract: 2000 children are born in the UK per year with a rare genetic syndrome with significantly increased morbidity and mortality (8). Little is known about growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves.This research will identify growth, developmental patterns and phenotypes in children with rare genetic syndromes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms. I will analyse social media content to see if I can use this to enrich the data available for clinicians. I will create an observational cohort of 500 children with rare genetic syndromes (GenROC) and address the following research objectives: Collate growth, development and medical profile of children with genetic syndromes (WP1.1) Generate growth curves for the 10 most frequently recruited syndromes (WP1.2) Link data for long-term medical and educational outcomes (WP1.3) Data exploration of social media groups for 10 syndromes to evaluate the quantity and quality of the information as a source of data for this study (WP21.) Assess the feasibility and acceptability of enriching: qualitative study with parents and stakeholders (WP2.2) Assess the utility of using this data for enrichment: proof of principle study to evaluate the change in diagnostic and predictive performance with additional data (WP2.3) Co-develop a consensus for a digital interface for gathering further data from (WP3.1) Co-produce a prototype based on WP3.1Methods: Work Stream 1 (WS1): Work Package (WP)1.1prospective and retrospective recruitment to GenROC (n=500); Utilise proforma (1,5,6) for clinician version and convert to lay terminology with PPI involvement for parent version. Analysis proformas and upload of phenotype and genotype data and pregnancy history to DECIPHER. WP1.2 Generate growth and developmental curves for at least 10 syndromes through DECIPHER.WP1.3 Link Data with national datasets (health and education) for outcomesWS2:WP2.1 Co-produce a parent questionnaire to map numbers of syndromes with a social media group and estimate coverage. Investigate coverage on social media by manual curation and correlate with analysis of questionnaire findings. Undertake natural language processing of websites and social media. WP2.2.1Ethics/data regulation: Series of one to one meetings culminating in expert workshop to formulate consensus agreement: GenEthics forum WP2.2.2 Qualitative study: Co-produce with PPI topic guide. Run 3 focus groups (6 parents each). Conduct qualitative semi structured discussions to assess acceptability and feasibility of proposed data enriching (analysed for themes). WP2.3.1 Extract information from websites for 10 syndromes: assess if identifiable/useful data can be refined from it using manual analysis and text analyticsWP2.3.2 Create simple portal for data uploads - consent parents to participation (all eligible from WS1). Analyse data using novel machine learning/data science to assess for clinical impact WS3: WP3.1 Digital Stakeholder meeting (3 researchers, 2 DECIPHER, 10 parents, 1 geneticist, 4 paediatricians) Present data from WS1/WS2. Determine consensus on best approach to using data to inform clinical practice.WP3.2 Co-production workshops (10 parents, 3 researchers) to develop prototype

Lay abstract: 2000 children per year are born in the UK with a rare genetic syndrome. Children with genetic syndromes have complex medical problems and require more medical appointments and hospital attendances than other children. These children often have developmental and learning difficulties and require extra support at school. There are almost 2000 genes that cause children to have developmental syndromes. Each syndrome will affect a small number of children and therefore research into individual syndromes is limited. We don't have enough information about these syndromes, so we don't know how these children grow and develop. Therefore doctors don't know how to monitor children with genetic syndromes, or which investigations and treatment they need. This means parents have formed syndrome-specific social media support groups where they gather and share information. Aim: This research aims to determine growth and development patterns, range of medical problems and long term medical and educational outcomes of children with rare genetic syndromes. It will discover if gaps in information can be filled in by working together with parents and social media groups to use information they are already gathering. Design/methods: I will gather information (height, weight, head circumference, birth weight, development progress and medical features) from about 500 children with rare genetic syndromes and follow them up. This is called an observational cohort. I will link this data to national databases to investigate long term outcomes. I will generate syndrome specific growth curves for at least 10 syndromes. I want to enrich this data using the data parents hold as well as the data on social media sites for rare genetic syndromes. I will a) talk to ethicists and data controllers about using this data. I hope to reach consensus (agreement) on how we do this, b) run 3 focus groups (6 parents each) on how families feel about us using this data, c) gather information from parents and social media sites. I will work with a software engineer to understand how this data could be used to improve our knowledge. I will develop an interface (prototype) for clinicians and patients. To ensure this is appropriate for both groups, I will a) hold a meeting of interested parties (digital stakeholders) made up of parents, geneticists, paediatricians and researchers to find out what sort of web interface would be most beneficial to all. b) We will co-produce a prototype in a series of two workshops (10 parents each).Patient and public involvement (PPI): Discussions with 9 parents confirmed the importance of this proposal and appropriate methods for recruitment. I will form a PPI group with 8-10 parents, meeting twice per year. I will form a group of representatives from key groups (stakeholder group), meeting 5 times during the fellowship. Dissemination: I will publish results in peer-reviewed journals and use a range of ways to convey information including lay summaries, blogs and social media for patient and public presentation. I will present results to national and international conferences and organisations for maximum impact.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;7.1 INDIVIDUAL CARE NEEDS
Health categories: DISPUTED AETIOLOGY AND OTHER