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 CAMK2 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 CAMK2 Syndrome (what symptoms and complaints are present, and when exactly do they arise) is of great importance 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 the CAMK2-related disorder is a new, recently discovered disorder, we still have insufficient insight into the main clinical features and how the disorder develops over time. We are currently gathering this information. The first international CAMK2 patient day was held in November 2019. Various specialists and paramedics collected as much information as possible from all patients present. Blood was also taken from everyone. This has been the start of the CAMK2 “Natural History” study. This study has a number of objectives:
- Making a patient registry for CAMK2-related conditions
- Making phenotype-genotype correlations (can we predict the severity based on the mutation)
- Generation of iPSC (Induced Pluripotent Stem Cells) from Blood for research. See the pre-clinical research page on this website for more information.
Rigter PMF, et.al. (2024) Role of CAMK2D in neurodevelopment and associated conditions. Am J Hum Genet. Pubmed
Rigter PMF, de Konink C, van Woerden GM. (2023). Loss of CAMK2G affects intrinsic and motor behavior but has minimal impact on cognitive behavior. Front Neurosci. Jan 6;16:1086994. Pubmed
Rigter PMF, et.al. (2022) Adult Camk2a gene reinstatement restores the learning and plasticity deficits of Camk2a knockout mice. Pubmed
Dwyer BK, et.al. (2022) Case Report: Developmental Delay and Acute Neuropsychiatric Episodes Associated With a de novo Mutation in the CAMK2B Gene (c.328G>A p.Glu110Lys) Front Pharmacol. 10;13:794008 Pubmed
Onori MP & van Woerden GM. (2021) Role of calcium/calmodulin-dependent kinase 2 in neurodevelopmental disorders. Brain Res Bull. S0361-9230(21)00090-3 Pubmed
Moro A, et.al. (2020) CaMKll controls neuromodulation via neuropeptide gene expression and axonal targeting of neuropeptide vesicles. PLoS Biol. Pubmed
Kool MJ, et al. (2019) CAMK2-dependent signaling in neurons is essential for survival. J Neurosci. 39; 5424–39. Pubmed
Vargas JY, et al. (2019) The Wnt/Ca 2+ pathway is involved in interneuronal communication mediated by tunneling nanotubes. EMBO J. Pubmed
Onori MP, et al. (2018) The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function. Hum Mutat. 39; 2008–24. Pubmed
Küry S, et al. (2017) De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet. 101; 768–88. Pubmed
Kool MJ, et.al. (2016) The molecular, temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in mouse locomotion. Sci Rep. Pubmed
Achterberg KG, et al. (2014) Temporal and region-specific requirements of αCaMKII in spatial and contextual learning. J Neurosci. 34; 11180–7. Pubmed
Woerden G, et.al. (2009) betaCaMKll controls the direction of plasticity at parallel fiber-Purkinje cell synapses. Nat Neurosci. 12(7); 823-5. Pubmed
Hojjati M, et.al. (2007) Kinase activity is not required for alphaCaMKll-dependent presynaptic plasticity at CA3-CA1 synapses. Nat Neurosci. 10(9); 1125-7. Pubmed
Hansel C, et.al. (2006) alphaCaMKll is essential for cerebellar LTD and motor learning. Neuron. 51(6); 835-43. Pubmed
Elgersma Y, et.al. (2004) Mouse genetic approaches to investigating calcium/calmodulin-dependent protein kinase ll function in plasticity and cognition. J Neurosci. 24(39); 8410-5. Pubmed
Elgersma Y, et.al. (2002) Inhibitory autophosphorylation of CaMKll controls PSD association, plasticity and learning. Neuron. 36(3); 493-505. Pubmed
Do you have questions about research at ENCORE? Or do you want to participate? Please contact us via encore@erasmusmc.nl or CAMK2disorders@erasmusmc.nl