Academic Center for Neuro-Developmental Disorders (ENCORE)

The primary aim of expertise center ENCORE (Erfelijke Neuro-Cognitieve Ontwikkelingsstoornissen, Rotterdam, ErasmusMC) is to improve the quality of life of patients with genetic neurodevelopmental disorders, through multidisciplinary specialized care, and preclinical, translational and clinical research.

Academic Center of Excellence

Research Activities

The research team of ENCORE is highly multidisciplinary representing 6 'core' departments** (of a total 13 departments involved in ENCORE) and covering multiple research levels.

Basic (preclinical) research: We make use of mouse models, hIPS cells and primary neuronal cultures to identify the mechanism underlying neurodevelopmental disorders and to identify treatments (e.g. 'Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model.' J.Clin.Invest, 2015).

Translational research: we have performed multiple investigator-initiated clinical trials in which we investigate novel treatment options.

These drugs are a direct result of our preclinical research activities, and the trials are unique in the field and have been published in high profile journals (e.g. 'Simvastatin for cognitive deficits and behavioural problems in patients with NF1; a randomised, placebo-controlled trial'; Lancet Neurol, 2013).

Clinical research: given that we have some of the largest patient cohorts in the world, we are currently performing several clinical research studies, addressing a wide variety of issues such as communication, sleep, epilepsy, behavioral problems, treatment of tumors (SEGAs, plexiform fibromas) etc. (e.g. Epilepsy in children with tuberous sclerosis complex: Chance of remission and response to antiepileptic drugs; Epilepsia 2015).

--------------------------------------------------------------------------------------------------------- ** IMPORTANT NOTE FOR ALL FOLLOWING QUESTIONS:

Founding 'core' departments: Kindergeneeskunde, Neurologie, Kinder- en Jeugd Psychologie en Psychiatrie, Klinische genetica, Neurowetenschappen en (volwassen) Psychiatrie.

Type of


We are closely collaborating with several international researchers. Some of these collaborations are formalized in networks such as ERARE and European Reference Networks (ERNs). ENCORE participates in the ERN ITHACA and GENTURIS.



ENCORE is highly involved in medical and basic research training. Besides participation in the medical curriculum we participate in: BSc training: ENCORE is involved in minor education through the depts. of Neurology, Neuroscience, Psychiatry and clinical genetics. At any given time ENCORE hosts around 10 BSc internship students, both clinical and preclinical. MSc training: We actively participate in the masters of Neuroscience (EMC) and have many internship students from other masters in the Netherlands as well as abroad.

At any give time ENCORE hosts around 10 MSc internship students within ENCORE, both clinical and preclinical. Lectures and workshops for MSc students are also given in Nijmegen, Amsterdam and Utrecht. PhD students: ENCORE has several PHD students (currently 9) who are doing pre clinical, translation or clinical research Subspecialism: Kindergeneeskunde - Erfelijke en aangeboren aandoeningen (EAA)": Pediatrics- inherited and congenital diseases is a subspecialty in pediatrics established by the Netherlands Association of Pediatrics (NVK). This subspecialty focusses on diagnosis, treatment and coaching of patients with hereditary and congenital diseases. EAA subspecialists participate in clinical/fundamental research and teaching at all levels within the medical curriculum.

Post-graduate training: ENCORE has organized several post-graduate activities (AVG, logopedie, psychiatry etc.) Medical training activities are subjected to formal evaluation tools including SET Q, and D-RECT. International students: Currently ENCORE has two Italian PhD students, one Romanian Postdoc, one Italian Postdoc and one Postdoc from Poland. We typically have several foreign master and bachelor students for short (6 month) internships, and visiting doctors from various countries. One of the Leading PI's is from the US. We frequently have visiting physicians who would like to 'copy' one of the multidisciplinary ENCORE clinics abroard.


Care Activities

Clinical care within the expertise clinics of ENCORE is 100% academic according to the ROBIJN model. Clinical pathways are well defined, and are all multi-disciplinary (within and between departments), involving a minimum of 2 specialists (but more commonly 3 or more).

Moreover, ENCORE typically provides paramedic care (speech therapist, physiotherapist, dietician, psychologist, psychotherapist etc.) The department CAPP is involved in the development and implementation of care and quality protocols. 'Zorgstandardaarden' en 'richtlijnen' have been (are in the process of being) developed for NF1, TSC, AS and FraX expertise centers With regard to value-based health care; Outcome measures are defined together with patient organisations and documented and monitored/evaluated.

For NF1 we are in the implementation phase of KLIK (Quality of life in the picture), i.e. guiding the outpatient consultation by quality of life outcomes as completed by (parents of) patients. If successful, this project will be extended to other ENCORE clinics Audits are implemented by defining annual goals and by setting up procedures for updating protocols and monitoring improvements. Although we have not performed official audits, all ENCORE clinics are now NFU recognised expertise centers, which required extensive documentation. For NF1 we are now in the phase of developing a care-network between our expertise center and the dedicated 'treatment' centers.

The NF1 patient organisation has developed a website a poll on quality assessment of all centers in the network aiming to improve the patient care. Also other patient organisations perform polls to monitor our quality and satisfaction of the parents. Research strongly contributes to ENCORE innovation and care.Clinical research is directly implemented into clinical care and guidelines, preclinical research is translated into clinical trials (see question 1) or into improved diagnostics (e.g. implementing functional assays).

Societal Relevance to Research, Education and Patient Care

Patient care and education, see sections about patient care and education.

Society: With its highly innovative basic and translational research, ENCORE provides a valuable contribution to innovation and medicine. Some of the findings on rare diseases can potentially be applied to a more generalized population, for instance with respect to treatment of epilepsy.

Economics: The development of treatments for these disorders will eventually result in an economical gain, since less intensive care will be needed. Moreover, ENCORE closely collaborates with pharmaceutical companies to identify and develop treatments. Research and education:

Knowledge dissemination ENCORE organizes workshops and symposia, and gives world-wide presentations for parent organizations. Guidelines: ENCORE has developed (or is in the process of developing) guidelines and care standards for all the rare disorders that are under the ENCORE umbrella. We also developed brochures for caregivers, teachers and children.

Viability of Research, Education and Patient Care

Continuity in care is maintained by striving for a minimum of 2 persons per specialism. For the core specialists this works out well. But with so many specialists and departments involved, we are certainly vulnerable at some of these positions. We are well aware of this and this is a recurring point on our agenda. Several of the leading investigators of ENCORE dedicate 100% of their time to research.

Hence, for the viability of research ENCORE has gathered sufficient mass to ensure sustained research lines for the next decade. Knowledge across ENCORE disciplines is shared by monthly joined meetings during which PhD students present their work. Several PhD students went aboard for several months or years, either as as a postdoc or resident. PIs and students participate frequently in international conferences. PhD students were actively involved in setting-up European networks. ENCORE is small enough to readily identify new talent.

Talented students are guided and stimulated as much as possible. This has resulted in personal fellowships (VENI, VIDI, VICI, EMC fellowship) and travel/short-stay fellowships, as well as cum laude PhDs. ENCORE has generated several publications in the top journals of the fields of the founding departments (JAMA, Lancet Neurology, Molecular Psychiatry, Nature Neuroscience, Nature Genetics).

Key and relevant publications of the last five years

  • Van Der Vaart et al. (2013) Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet Neurol 12, 1076–1083
  • Bruinsma et al. (2015) Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model. J Clin Invest 125, 4305–4315
  • Goorden et al., (2015) Intact neuronal function in Rheb1 mutant mice: implications for TORC1-based treatments. Hum Mol Genet. 24, 3390–3398.
  • De Esch et al. (2015) Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test. Neurobiol Dis 75, 31–39
  • Omrani et al. (2015) HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1. Mol Psychiatry 20, 1311–1321
  • Elgersma (2015) Neurodevelopmental disease: A molecular tightrope. Nature 526, 50–51
  • Silva-Santos et al. (2015) Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model. J Clin Invest 125, 2069–2076
  • Van Der Vaart et al, (2016) Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1. Neurology 86:154–160.
  • Overwater et al, (2016) Genotype and brain pathology phenotype in children with tuberous sclerosis complex. Eur J Hum Genet 24:1688–1695.
  • Overwater et al, (2017) Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex. J Neurol 264:161–167.
  • Onori MP, et al, (2018) The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function. Hum Mutat.

PhD theses of the last five years

  • A.S. (Andreea) Pop (10-04-2013) Fragile X syndrome: Steps towards therapy
  • S.M.I. (Susan) Goorden (29-02-2012) Unraveling the molecular and cellular mechanisms of neurological dysfunction in Tuberous Sclerosis Complex
  • C.F. (Caroline) Bruinsma (03-05-2016) The Role of UBE3A in Motor- and Cognitive Function
  • M.H.T. (Thijs) Van der Vaart (22-09-2015) Translational research on targeted treatment for cognitive deficits in neurofibromatosis Type 1
  • C.E.F. de Esch (25-06-2014) Therapeutic targets and translational endpoints in fragile X syndrome
  • M.E.C. (Marije) Meuwissen (02-04-2014) Genetic causes of cerebrovascular disorders in childhood
  • A.M. (Agnies) van Eeghen (17-12-2013) Identifying Determinants for Neurobehavioral Morbidity in Tuberous Sclerosis Complex
  • C.J. (Cathryn) Poulton (26-06-2013) Genes and mechanisms in primary microcephaly.
  • R. (Renske) Oegema (10-05-2016) Malformations of cortical development: clinical and genetic characterization.
  • R.A.M. Buijsen (2016) Fragile X-associated Tremor/ Ataxia Syndrome: RNA or RAN?

Non-scientific publications related to the ACE

  • Onderzoek: middel bij neurofibromatose. De Telegraaf (2015)
  • Epilepsiemiddel helpt brein. Volkskrant (2015)

Principal coordinator(s)

Last updated: 365 days ago.