P371: Pathogenic variant in DACH1 may cause a new neurodevelopmental syndrome with hearing loss and nephropathy

families had children with ASD with discordant cognitive impairment.De novo variants were identified in the proband with cognitive impairment (DDX3X, n=1; FBXW7, n=1).Sanger sequencing confirmed these variants were absent in the comparator sibling with ASD without cognitive impairment.Definitive diagnoses resulted in one or more changes in management in 50% (5/10) including eligibility for targeted therapy (n=1), tumor surveillance (n=1), specialist referral (n=3).Four children (12%) had additional clinically significant findings unrelated to ASD.Conclusion: Genome sequencing is effective to identify both common and more rare genomic disorders in young children with ASD and cognitive delays.cGS could be considered as a first-line genetic testing, particularly in children with complex phenotypes.This study adds to the growing literature supporting genome-wide sequencing in children with neurodevelopmental disorders.