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Objectives Current guidelines for genetic testing in childhood-onset diabetes focusses on Maturity Onset Diabetes of the Young (MODY) or rare genetic syndromes and children with diabetes and unclear or isolated additional clinical features are often not tested.1 We aim to determine whether routine genetic testing should be recommended for children with diabetes and additional syndromic features and assess if novel biomarker, type 1 diabetes genetic risk score, can help to select children for genetic testing. Methods We conducted a study of 1093 children with diabetes across seven paediatric diabetes clinics. The diabetes related clinical features, islet autoantibody status and additional non-autoimmune extra-pancreatic features were recorded. We generated 30 variants type 1 diabetes genetic risk score (T1D-GRS).2 3 All children with syndromic diabetes had targeted next-generation sequencing to analyse all known dominant and recessive genes causing monogenic diabetes.4 Results Among the 1093 participants, 68 (6.2%) children had diabetes with additional non-autoimmune extra-pancreatic features. In this syndromic cohort, 22% (15/68) found to have monogenic diabetes. The most common causes were WSF (n=3, 20%) and SLC19A2 (n=3, 20%). Of the 30/68 children with high T1D-GRS (>50th centile of T1D population), only 1 (1/30, 3%) was found to have monogenic diabetes compared to 14 (14/38, 37%) of the children with low T1D-GRS (Conclusion One in five children with diabetes and additional non-autoimmune features have monogenic diabetes. Many of these children do not display features in keeping with typical clinical syndromes and clinician predictions often fail to identify these cases. T1D-GRS is a useful, novel biomarker in these children. Our study recommends routine genetic testing for all children presenting diabetes alongside additional syndromic features. This approach can enable personalised and precise management strategies, ultimately leading to improved patient outcomes. References Hattersley et al. ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents 2018. Patel et al. Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes 2016. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls, The Wellcome Trust Case Control Consortium 2007. Patel et al. Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics 2022.
Myers et al. (Tue,) studied this question.