CAMK2-related Synapthopathies Natural History Study

NCT07372833 | Recruiting DMC

• 1 other identifier: MEC-2021-0099
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The key endpoint for this prospective cohort study is: Mapping of the disease course of all known patients (both children and adults, international) with a CAMK2 mutation, for which ENCORE has founded an expert clinic, and therefore has a substantial and active neuroscientific research arm combined with tertiary academic clinical care delivery for those living in the Netherlands. Such robust clinical maps can subsequently be used for genotype-phenotype correlations and, identify clinically relevant outcome measures for prognostication, improvement of care delivery \& future clinical trials. Additionally, it will most likely generate new research questions for basic scientists who are trying to unravel the specific mechanisms of disease pathophysiology.

Conditions

CAMK2; Calcium/Calmodulin-dependent Protein Kinase 2

Keywords

CAMK2; Calcium/calmodulin-dependent protein kinase 2

Outcome Measures

Primary Outcomes (5)

• Age of milestone achievement

  The TAND (Tuberous Sclerosis Associated Neuropsychiatric Disorders) Checklist collects information on the age at which developmental milestones were achieved, enabling the creation of CAMK2-specific developmental curves.

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years.

• Presence of seizures

  Presence of seizures is evaluated through our General questionnaire, which inquires about the presence of comorbidities, and through the online medical interview.

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Adaptive Behavior Assessment System 3 (ABAS-3) score

  The General Adaptive Composite (GAC) score of the ABAS-3 provides an overall estimate of adaptive functioning. Additionally, scores on the different subdomains of the ABAS-3 can be compared with developmental age. The questionnaire consists of 10 subdomains, each with a minimum score of 0 and a maximum score ranging from 66 to 78. Higher scores indicate higher developmental levels.

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Social Responsiveness Scale, Second Edition (SRS-2) total score

  The SRS-2 measures the severity of social impairment associated with autism spectrum disorder, as individuals with CAMK2-related disorder often exhibit autism spectrum traits. The score from this questionnaire ranges from 0 - 195. For school-aged individuals, scores of 57 and lower are considered to be within normal limits, for pre-school-aged individuals scores of 66 and lower are considered to be within normal limits. Higher scores indicate higher deficiencies in reciprocal social behavior.

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Aberrant Behavior Checklist (ABC) score

  The Aberrant Behavior Checklist measures problem behaviors in individuals with intellectual and developmental disabilities. Scores range from 0 - 174, with higher scores indicating more overall behavioral challenges.

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

Secondary Outcomes (7)

• Repetitive Behaviors Questionnaire (RBQ) score

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Child Behavior Checklist (CBCL) score

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Children's Behavior Questionnaire (CBQ) score

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Mood, Interests and Pleasure Questionnaire Long form (MIPQ-L) score

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

• Short Sensory Profile (SSP) score

  At baseline and again at the following key developmental ages that have not yet been reached: 3-4 years, 6-7 years, 11-12 years, and 15-17 years. After age 18 years, assessments are repeated every 5 years.

Study Arms (1)

CAMK2 mutation

Patients with a mutation in the CAMK2A, CAMK2B, CAMK2D and CAMK2G gene.

Other: No intervention

Interventions

No intervention OTHER

This is an observational study without interventions.

CAMK2 mutation

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

National and international children and adults with a (likely) pathogenic variation in one of the CAMK2 genes.

You may qualify if:

• Subject with a (likely) pathogenic variation in one of the CAMK2 genes
• Consent for anonymous registration in an (inter)national database

You may not qualify if:

• \- Subjects with a Variant of Unknown Significance (VUS); in those cases functional analysis should be performed first.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biobank for induced pleuripotent stem cells.

Study Officials

• Danielle CM Veenma, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle CM Veenma, MD PhD

CONTACT

010-7037815; camk2disorders@erasmusmc.nl

Anjuli L Dijkmans, MD

CONTACT

camk2disorders@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor, MD PhD

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: January 28, 2026
• Study Start: February 9, 2021
• Primary Completion (Estimated): January 1, 2040
• Study Completion (Estimated): January 1, 2040
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

NL (1)