CAMK2-related Synapthopathies Natural History Study

Natural History Data of International Subjects With an ULTRA-Rare Neuro Developmental Disorder as Part of the ENCORE Expert Clinics, Specifically CAMK2A, CAMK2B, CAMK2D, and CAMK2G.

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.

Study Overview

• Status: Recruiting
• Conditions: CAMK2; Calcium/Calmodulin-dependent Protein Kinase 2
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Danielle CM Veenma, MD PhD; Phone Number: 010-7037815; Email: camk2disorders@erasmusmc.nl
• Study Contact Backup: Name: Anjuli L Dijkmans, MD; Email: camk2disorders@erasmusmc.nl

Study Locations

• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus MC
      • Contact: Danielle CM Veenma, MD PhD; Phone Number: 010-7037815; Email: camk2disorders@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CAMK2 mutation; Patients with a mutation in the CAMK2A, CAMK2B, CAMK2D and CAMK2G gene.	Other: No intervention; This is an observational study without interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repetitive Behaviors Questionnaire (RBQ) score	The RBQ measures restricted and repetitive behaviors. Scores range from 0 - 76, with higher scores indicating higher frequency of restricted and repetitive 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.
Child Behavior Checklist (CBCL) score	The CBCL measures emotional and behavioral problems. The questionnaire assesses internalizing problems, externalizing problems, and other problems. For children aged 1.5-5 years, scores for internalizing problems range from 0-72, scores for externalizing problems range from 0-48, and scores for other problems range from 0-14. For the 6-18-year-old group, scores for internalizing problems range from 0-64, for externalizing problems from 0-70, and for other problems from 0-72. Higher scores indicate greater problems in these domains.	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	The Children's Behavior Questionnaire (CBQ) measures temperament in early childhood. Subdomains consist of presence of self-injury, severity of self-injury, physical aggression, destruction of property and stereotyped behaviors. Scores range from 0 - 18, with higher scores indicating higher severity of problems.	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	The Mood, Interests and Pleasure Questionnaire monitors emotional well-being and quality of life through subscale scores of mood, interest and pleasure. Scores range from 0-100, with higher scores indicating more positive mood, interest, and pleasure	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	The Short Sensory Profile questionnaire measures sensory processing patterns. Scores range from 0 - 185, with lower scores indicate more frequent sensory processing difficulties.	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.
Sleep questionnaire for children with neurological andother complex illnesses (SNAKE) score	The SNAKE questionnaire for children with severe psychomotor impairments measures sleep problems in children with severe neurological or psychomotor disabilities. Scores range from 23 - 92, with higher scores indicating more frequent and/or more severe sleep disturbances.	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.
Presence of loss of skills	The LOST-skill questionnaire inquiries about skills in all areas of development and functioning, and stability of body functions, in order to identify patterns of skill loss. Scoring is not used in this questionnaire, as the questionnaire aims to identify patterns.	Assessment with this questionnaire begins at ages 15-17 and is repeated every five years thereafter.

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Danielle CM Veenma, MD PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2021
• Primary Completion (Estimated): January 1, 2040
• Study Completion (Estimated): January 1, 2040

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: January 23, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: CAMK2; Calcium/calmodulin-dependent protein kinase 2
• Other Study ID Numbers: MEC-2021-0099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided at the moment

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No