UNIQUE (rare autism spectrum disorders)

In order to provide the best possible care to patients with a rare condition, it is essential that global knowledge about the condition is gathered. Nationwide, centers of expertise have been set up to stimulate care for rare disorders and to gather knowledge. For the formal recognition of an expertise center by the Ministry of Health, an important condition is that the expertise center gathers, analyzes and shares knowledge through publications. These can be publications in scientific journals, but also treatment guidelines for health care professionals or information brochures for patients or caregivers. We optimize care and research within ENCORE through standardized follow-up and close collaboration between doctors and researchers. That way, we can ultimately develop better treatments for rare conditions. You may therefore be asked to participate in research. Participation in research is always on a voluntary basis. The data obtained is stored and analyzed in an anonymous form. All research has been approved in advance by an ethics review committee.

A genetic diagnosis has already been established for all patients seen in our UNIQUE expertise center. This genetic knowledge helps us to counsel the parents, and to better understand the effect of the genetic change ("mutation") on the severity of the symptoms. We can then also investigate which treatment works best for a particular genetic change. In some cases, the effect of the genetic change is unknown. In these cases, the genetic change will be further investigated in the laboratory (see preclinical research). You may be asked to provide a tube of blood for research. This blood is used to generate iPSC (induced Pluripotent Stem Cells). Brain cells can be grown from these iPS cells for research. See the pre-clinical research page on this website for more information on iPS research.

Detailed knowledge about the course of rare genetic forms of autism spectrum disorders (ASD) is of great importance in order to be able to recognize complaints early in the future and to treat them optimally. In addition, this is of great importance for drug research (trials). We will not only limit ourselves to the autism characteristics, but we will, in collaboration with the other specialisms within ENCORE and Erasmus MC-Sophia, also make an inventory of other common (physical / psychological) problems. Everyone who registers with UNIQUE is therefore asked to participate in medical scientific research.

In addition to providing care (diagnostics and counseling), the goal is to set up a biobank and database with phenotypic data (observable traits) and genetic data. In the long term, these will give us the opportunity to investigate the genetic disorders, their influence on the social and physical functioning of these people and the underlying biological mechanisms. We also hope to learn more about the genetic background of autism spectrum disorders (ASD) in the broad sense. Collaborations with other (national and international) centers will be initiated to collect as much data as possible with combined forces. This gives us the opportunity to provide parents and patients with a rare genetic disorder (either a known syndrome or an unknown genetic variant) and characteristics of ASD with more insight into the symptoms, the course of the disorder and new treatment methods in the future.

The scientific research at UNIEK takes approximately 1 hour and 10 minutes (with a maximum of 6 hours, depending on the amount of information that has been collected earlier and can be retrieved) and takes place at the outpatient clinic Child and Adolescent Psychiatry and Psychology of Erasmus MC-Sophia. If a visit to the hospital is too stressful, it is possible to have the visit take place in the Sophia bus, a camper that is equipped as a mobile examination room. You can then choose a suitable place where the visit will take place.
During the examination, a tube of blood may be taken, and various tasks and (computer) games are done. Brain activity is measured using a technique called fNIRS (functional Near Infrared Spectroscopy). This is a very (child) friendly technique in which participants wear a cap with lights on their head. Eye movements (eye tracking) are registered by a camera in a computer screen that measures what the participant is looking at. A 3D photo is also made of the face (3dMD technique). In addition, we would like to perform some cognitive/behavioral tests or use the data from previous tests. In case the participant is a child, we also ask the parents and sometimes a teacher to complete a number of questionnaires.

Our brains use oxygen when they are active. This oxygen is supplied by the body through the blood. When the body senses that there is a great need for oxygen in a certain area, extra oxygenated blood is transported to the active area. This changes the ratio between oxygen-rich and oxygen-poor blood in the brain and we can measure this. We do this with the help of a technique called fNIRS (functional Near-Infrared Spectroscopy). The technique uses near-infrared (near-infrared) light signals. By placing a kind of bathing cap with points of light on the scalp in certain places and measuring how the light is reflected by the blood in the brain, it can be determined how much blood flows through the brain and which part of it is low or high in oxygen. This way we can determine which brain areas are active.

Eye tracking
Eye tracking analysis makes use of the notion that we focus longer on images that are interesting or complicated. Saccades, a short period in which we cannot see, and fixations, a longer period in which we focus our attention and eyes on something, are often used in eye-tracking research.
In eye-tracking research, the participants play games or perform tasks on a computer. For this research we use the Tobii Pro TX300, a screen-based eye tracker. This measures what the eyes are looking at on the screen. The participants do not notice this. While performing these tasks, brain activity will also be measured with fNIRS.

3dMD Scan
With a 3dMD scanner, facial features can be recorded in a quantitative way. The 3dMD face scanner uses two pairs of cameras on a large tripod. The cameras create a 180 degree 3D image of the face with real looking skin texture and skin color. During registration, two projectors project random light patterns on the face. The device uses them as a guide for making the image. The process is usually very short, with a maximum of 20 seconds per registration. This means that taking a 3D photo together only takes a few minutes. After scanning, the system automatically generates a 3D image.

Albuainain F, et.al. (2024) Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder. Eur J Hum Genet. Pubmed

Heimer G, et al. (2020) Netrin-G2 dysfunction causes a Rett-like phenotype with areflexia. Hum Mutat 41, 476–86. Pubmed

Kumar R, et al. (2020) Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor. Front Mol Neurosci. 13,1-15. Pubmed

de Vrij FM, et al. (2019) Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia. Mol Psychiatry. 24; 757–71. Pubmed

White T, et al. (2018) Paediatric population neuroimaging and the Generation R Study: the second wave. Eur J Epidemiol. 33; 99–125. Pubmed

Bruinsma CF, et al. (2015) An essential role for UBE2A/HR6A in learning and memory and mGLUR-dependent long-term depression. Hum Mol Genet. 25; 1-8. Pubmed

Eussen, M.L. et al. (2013) The association of quality of social relations, symptom severity and intelligence with anxiety in children with autism spectrum disorders. Autism 17, 723–735. Pubmed

Marroun, El, H. et al. (2013) Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children. Neuropsychopharmacology. Pubmed

Louwerse, A. et al. (2013) Autonomic Responses to Social and Nonsocial Pictures in Adolescents With Autism Spectrum Disorder. Autism Res. Pubmed

So, P. et al. (2013) Using the Child Behavior Checklist and the Teacher’s Report Form for identification of children with autism spectrum disorders. Autism 17, 595–607. Pubmed

Román, G.C. et al. (2013) Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. Pubmed

Greaves-Lord, K. et al. (2013) Empirically based phenotypic profiles of children with pervasive developmental disorders: interpretation in the light of the DSM-5. J Autism Dev Disord 43, 1784–1797. Pubmed

White, T. et al. (2013) Pediatric population-based neuroimaging and the Generation R Study: the intersection of developmental neuroscience and epidemiology. Eur. J. Epidemiol. 28, 99–111. Pubmed

Jaspers, M. et al. (2013) Early childhood assessments of community pediatric professionals predict autism spectrum and attention deficit hyperactivity problems. J Abnorm Child Psychol 41, 71–80. Pubmed

Baudouin, S.J. et al. (2012) Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 338, 128–132. Pubmed

van der Vlugt, J.J.B. et al. (2012) Cognitive and behavioral functioning in 82 patients with trigonocephaly. Plast. Reconstr. Surg. 130, 885–893. Pubmed

Hermans, H. et al. (2012) Feasibility, reliability and validity of the Dutch translation of the Anxiety, Depression And Mood Scale in older adults with intellectual disabilities. Res Dev Disabil 33, 315–323. Pubmed

Vuijk, R. et al. (2012) Personality traits in adults with autism spectrum disorders measured by means of the Temperament and Character Inventory. Tijdschr Psychiatr 54, 699–707. Pubmed

Nijmeijer, J.S. et al. (2010) Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD. J Child Psychol Psychiatry 51, 1242–1250. Pubmed

Tiemeier, H. et al. (2010) Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study. Neuroimage 49, 63–70. Pubmed

de Bruin, E.I. et al. (2009) Autistic features in girls from a psychiatric sample are strongly associated with a low 2D:4D ratio. Autism 13, 511–521. Pubmed

Herba, C.M. et al. (2008) Face and emotion recognition in MCDD versus PDD-NOS. J Autism Dev Disord 38, 706–718. Pubmed

de Bruin, E.I. et al. (2007) Multiple complex developmental disorder delineated from PDD-NOS. J Autism Dev Disord 37, 1181–1191. Pubmed

de Bruin, E.I. et al. (2007) High rates of psychiatric co-morbidity in PDD-NOS. J Autism Dev Disord 37, 877–886. Pubmed

de Bruin, E.I. et al. (2006) Differences in finger length ratio between males with autism, pervasive developmental disorder-not otherwise specified, ADHD, and anxiety disorders. Dev Med Child Neurol 48, 962–965. Pubmed

de Bruin, E.I. et al. (2006) WISC-R subtest but no overall VIQ-PIQ difference in Dutch children with PDD-NOS. J Abnorm Child Psychol 34, 263–271. Pubmed

Dekker, M.C. et al. (2002) Assessing emotional and behavioral problems in children with intellectual disability: revisiting the factor structure of the developmental behavior checklist. J Autism Dev Disord 32, 601–610. Pubmed

van der Geest, J.N. et al. (2002) Gaze behavior of children with pervasive developmental disorder toward human faces: a fixation time study. J Child Psychol Psychiatry 43, 669–678. Pubmed

van der Geest, J.N. et al. (2002) Looking at images with human figures: comparison between autistic and normal children. J Autism Dev Disord 32, 69–75. Pubmed

Do you have questions about research at ENCORE? Or do you want to participate? Please contact us via encore@erasmusmc.nl or uniek@erasmusmc.nl