Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC): a study protocol

Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality(1). Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses. Methods and analysisThis is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the NHS and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again one year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least ten groups expected). The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication. Article SummaryStrengths and Limitations of this study O_LIThis study is a collaborative effort which combines previous data with that of a large cohort to maximise possible outputs through the DECIPHER database. C_LIO_LIThe study is the first of its kind to acquire natural history clinical data from a large cohort across the UK to ascertain both gene specific data but also cross syndrome cohort metrics. C_LIO_LIThe study utilises the Musketeers Memorandum to facilitate recruitment from genetics centres across the UK and also empowers families to volunteer directly which will be supported by a national patient support charity. C_LIO_LIThis study does not recruit individuals over the age of 15 and so longer-term outcomes will not be evaluated. Further studies of older individuals will be required to gather their data and we hope that a follow-on study would be possible to enable this. C_LIO_LIData are largely gathered through online questionnaires completed by both parent and clinician. The quality of data received will vary depending on the user. This method of data collection may result in selection bias against certain demographic groups which will need to be accounted for in any discussion regarding the generalisability of the results. C_LI