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.
Genetic testing will be performed on all Brain overgrowth syndrome patients seen in our center of expertise to determine the genetic cause and to be able to support and advise the parents. If genetic testing has already been done elsewhere, it will not be repeated. This genetic knowledge also helps us to better understand the effect of the genetic change ("mutation") on the severity of symptoms. We can then also investigate which treatment works best for a particular mutation. In rare cases, the genetic analysis is inconclusive. In these cases, the genetic change will be further investigated in the laboratory.
Detailed knowledge about the course of brain overgrowth syndromes (which symptoms and complaints are there, and when exactly do they arise) is of great importance in order to recognize complaints early and treat them optimally. In addition, this is of great importance for drug research (trials). After all, only if we can demonstrate that a new drug improves the quality of life compared to an untreated patient, will the drug actually be approved and reimbursed. Because there are many differences between the brain overgrowth syndromes, it is very important to gain insights into the course, the risks and the effects of (new) treatments. For this we also work together with doctors abroad. We will examine on an individual basis whether a targeted treatment is possible. We will ask for your permission to include information about your child in our database.
In addition to permission to record these clinical data, you may be asked to provide a tube of blood for research. This blood is used to generate iPSC (induced Pluripotent Stem Cells) for research. Brain cells can be grown from these iPS cells. See the pre-clinical research page on this website for more information about iPS research.
Recently, the doctors of the ENCORE center of expertise for cerebral overgrowth syndromes worked with a group of international colleagues on a 'guideline' for the follow-up and treatment of children with PIK3CA-related overgrowth syndrome (PROS). We will further develop the advice from this publication in the care path for children with PROS within the Sophia Children's Hospital. In this rare syndrome, how mild or severe the symptoms appear in each child varies greatly. We will therefore tailor-make treatment for each child, in consultation with parents.
Mancini GMS, et.al. (2021) Multidisciplinary interaction and MCD gene discovery. The perspective of the clinical geneticist. Eur J Paediatr Neurol. 35:27-34 Pubmed
Douzgou S, et.al. (2021) A standard of care for individuals with PIK3CA-related disorders: An international expert consensus statement. Clin Genet. Pubmed
Besterman AD, et.al. (2021) Functional and structural analyses of novel Smith-Kingsmore Syndrome-Associated MTOR variants reveal potential new mechanisms and predictors of pathogenicity. PLoS Genet. 17(7):e1009651. Pubmed
Proietti Onori M, et.al. (2021) RHEB/mTOR hyperactivity causes cortical malformations and epileptic seizures through increased axonal connectivity. PLoS Biol. 19(5):e3001279. Pubmed
Reijnders M, et.al. (2017) Variation in a range of mTOR related genes associated with intracranial volume and intellectual disability. Nat Commun. 8(1); 1052. Pubmed