GRIA) GRIN Intracellular calcium-related synaptopathy (CAMK2
Conditions
Interventions
None listed
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Age >18 years old - Genetic testing confirming a pathogenic variation (using international ACMG criteria) resulting in an intracellular calcium-related synaptopathy (CAMK2, GRIN, GRIA). For the proof-of-concept study we start recruiting patients with a mutation in either the CAMK2B (Pro139Leu) or CAMK2A (Thr286Xvariants) gene. - Able to provide written informed consent by a biological parent and/or legal representative. - Caregivers are sufficiently proficient in either Dutch, English, French or Spanish in order to complete questionnaires.
Exclusion criteria
Exclusion criteria: - Unable to understand or comply with the test circuit at the discretion of the treating physician (this concerns the parents of the patients as all are incapacitated). - Patients with more than 1 genetic diagnosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint 1 Feasible outcome measures for follow-up & intervention trials Identify a minimum of four CBL assessments that can capture patient*s main clinical symptoms up into adulthood. Our pilot data -using both caregivers and health care professionals as a source- indicates that the following measurements hold promise: o EEG background pattern (spectral analysis for the alpha, beta and theta bands during resting and upon social and non-social videos. Spectral analysis is a standard method for quantification of the EEG) and has been shown to be altered in children with neurodevelopmental disorders [e.g. Hipp 2021, Frohlich 2019]. o Score on eye-tracking tasks (social paradigms) # o ERP (auditive Event-Related Potential) # o Communication skill measures o OCT (retinal nerve layer thickness) o Motor function (standing balance, gait deviation index) o 24-hour movement behavior including sleep (activity tracker) o Growth parameters (including head circumference), body composition and facial shape (3D photography measures) *For the proof-of-concept cohort, we expect adult patients to have a developmental age younger than 4 years. However, assessments can be adjusted to any developmental age using the standard CBL protocol. # Measurements performed in combination with EEG Primary endpoint 2 Create detailed and standardized natural history data of adults with intracellular calcium-related synaptopathies to be used for primary aim 1 and secondary endpoint 2, in addition to provide better counseling of caregivers about prognosis and for the design of intervention studies. Once we have obtained a core set of assessments, we can expand this to other CAMK2 expertise centers around the world. Together with the parent organization, we are focusing on building a network of expertise centers, starting with North America. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoint 1 Create shared and disease-specific developmental curves with relevant and meaningful outcomes across four domains (cognition, behavior & language, neurophysiology, brain & craniofacial structure, and motor development) in children with intracellular calcium related synaptopathies, both from well-established and validated parameters in addition to newly developed parameters. This requires integration of parameters collected in time. We will start with outcomes in the domains cognition, behavior, language, and sleep. Secondary endpoint 2 Develop biomarkers from neurophysiological, gait analyses, MRI metrics, 3D photogrammetry, and OCT data in collaboration with researchers from TU Delft that can be used to predict long term development. This will be part of the larger CBL initiative to use machine learning algorithms (both classic and more advanced neural network-based methods) to identify new biomarkers. The multi-domain nature of the data (OCT, EEG, patient reports, etc.) will allow to apply multi-modal types of AI algorithms, which will be trained on integrated information from different measurement modalities. | — |
Countries
Netherlands
Outcome results
None listed