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.
| Original language | English |
|---|---|
| Journal | Journal of Child Psychology and Psychiatry and Allied Disciplines |
| Volume | 60 |
| Issue number | 3 |
| Pages (from-to) | 305-313 |
| Number of pages | 9 |
| ISSN | 0021-9630 |
| DOIs | |
| Publication status | Published - 01.03.2019 |
| Externally published | Yes |
Funding
Hospital de Clínicas José de San Martín, Universi-dad de Buenos Aires, Buenos Aires, Argentina; 7Division of Genetics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 8Department of Medical Genetics, Reference Center for Skeletal Dysplasia, INSERM UMR 1163, Laboratory of Molecular and Physiopathological Bases of Osteo-chondrodysplasia, Paris Descartes-Sorbonne Paris Cité University, AP-HP, Institut Imagine, and Hôpital Universitaire Necker-Enfants Malades, Paris, France; 9Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; 10Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands; 11MRC Human Genetics Unit, IGMM, Western General Hospital, Edinburgh, United Kingdom; 12Department of Health Sciences, Medical Genetics, University of Milan, Milan, Italy; 13Institut fu€r Humangenetik Lu€beck, Universita€tsklinikum Schleswig-Holstein, Lu€beck, Germany; 14Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India;15Department of Pediatrics Amsterdam UMC location AMC, University of Amsterdam, Amsterdam, the Netherlands; 16Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; 17Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands; 18Institute for Medical Genetics and Human Genetics, Charité – Univer-sita€tsmedizin Berlin, corporate member of Freie Universita€t Berlin, Humboldt-Universita€t zu Berlin, and Berlin Institute of Health, Berlin, Germany; 19Prinsenstichting Institute, Purmerend, the Netherlands; 20Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Rad-boud University Medical Center, Nijmegen, the Netherlands; 21Section for Functional Genetics, Institute of Human Genetics, University of Lu€beck, Lu€beck, Germany; 22Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 23Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 24Cerebra Centre for Neurodevelopmental Disorders, School of Psychology, University of Birmingham, Birmingham, United Kingdom; 25Institute of Cognitive Neuroscience, University College London, London, United Kingdom; 26Unidad de Genética Clínica y Genómica Funcional, Facultad de Medicina, Universidad de Zaragoza, IIS Aragón, Zaragoza, Spain; 27Unidad de Genética Clínica, Servicio de Pediatría, Hospital Clínico Universitario ‘Lozano Blesa’ CIBERER-GCV02 and Departamento de Pediatría, Facultad de Medicina, Universidad de Zaragoza, IIS Aragón Zaragoza, Spain; 28Division of Human Genetics, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 29Molecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy; 30UOC Pediatria, ASST Lari-ana, Como, Italy; 31Severinus Institute, Veldhoven,
Research Areas and Centers
- Research Area: Medical Genetics
DFG Research Classification Scheme
- 2.22-03 Human Genetics