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 Costello - CFC 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 Costello - CFC Syndrome (what symptoms and complaints are there, and when exactly do they arise) is of great importance in order to be able 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. We also use this information to create guidance for the treatment of Costello - CFC Syndrome.
In addition to recording 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.
Gripp KW, et al. (2019) Costello Syndrome: Clinical phenotype, genotype, and management guidelines. Am J Med Gent A. 179 (9); 1725-1744. Pubmed
Schreiber J, et al. (2017) Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models. Sci Rep. Pubmed
Wang T, et.al. (2015) In vivo synaptic transmission and morphology in mouse models of tuberous sclerosis, Fragile X syndrome, Neurofibromatosis type 1, and Costello syndrome. Front Cell Neurosci. Pubmed
Beukers, W. et al. (2013) HRAS mutations in bladder cancer at an early age and the possible association with the Costello Syndrome. Eur J Hum Genet DOI: 10.1038/ejhg.2013.251. Pubmed
Krab, L.C. et al. (2008) Oncogenes on my mind: ERK and MTOR signaling in cognitive diseases. Trends Genet 24, 498–510. Pubmed
Kushner, S.A. et al. (2005) Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway. J Neurosci 25, 9721–9734. Pubmed