Development, behaviour and autism in individuals with SMC1A variants

Abstract

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 SMC1A variants. Methods We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. 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 NIPBL variants. For Dutch participants with SMC1A variants we performed direct in‐person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett‐like phenotype show more severe intellectual disability and 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.

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

“…Cognitive functioning, developmental milestones and behavioral functioning in the RAD21 group are attenuated compared to the NIPBL and SMC1A groups (Tables 3 and S4). The majority of RAD21 patients (16/29, 55%) have normal or mildly impaired cognitive functioning (SMC1A group 32%; NIPBL group 7%) (Huisman et al, 2017;Mulder et al, 2019). In all three groups, there is a trend towards more language-based problems than motor-based problems in development.…”

“…Periodic formal screening for neuropsychological and behavioral problems is still warranted in all individuals with RAD21 variants, to allow for early recognition of problems and access to relevant support systems. In addition, formal (inperson) assessments can prevent misdiagnoses, such as autism, by putting behavioral characteristics into the perspective of the developmental level of patients (Mulder et al 2019).…”

“…To compare the RAD21 phenotype to CdLS patients with variants in other genes, clinical data were obtained from existing NIPBL and SMC1A cohorts (Huisman et al 2017;Mulder et al 2019), to which we added further information if needed. For comparison of features of ASD and aggression in NIPBL patients, we derived information from the UK cohort .…”

“…Cognitive and behavioral characteristics of individuals with RAD21 variants with sufficient clinical data (cohort A) with those in individuals with SMC1A and NIPBL variants [adapted from(Huisman et al 2017;Moss et al 2017;Mulder et al 2019)] …”

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes

“…[18,19]). The degree to which ASD-related behaviours present in excess of what may be expected for developmental level has been debated for a number of syndrome groups (see [20]). In the case of PTHS, comparison with matched-ability groups with other genetic syndromes may help elucidate the possible presence and nature of ASD-related behaviours.…”