Development, behaviour and autism in individuals with SMC1A variants

Introduction: Development and behaviour in Cornelia de Lange Syndrome(CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1Avariants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1Avariants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour(SIB) are compared to those in individuals with CdLS caused by NIPBLvariants. For Dutch participants with SMC1Avariants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviourand sensory processing. Results: Individuals with SMC1Avariants show a higher cognitive level and less SIB than individuals with NIPBLvariants. Individuals with SMC1Avariants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disabilityand more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.