Natural History Study of Infants and Children With CNKSR2-Associated Neurodevelopmental Disorders and Epilepsy
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Developmental Dysphasia
- Sponsor
- University of California, San Francisco
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Change from baseline in resting state background brain activity during sleep as measured by phase lag index using electroencephalography (EEG).
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This prospective natural history study is being conducted to define the electroclinical, neurodevelopmental, and behavioral characteristics of CNKSR2 epilepsy aphasia syndrome (EAS) and intellectual disability (ID) in children aged 6 to 21 years old with CNKSR2 mutations.
The data collected from this study will serve as an external control to eventual clinical trials examining precision medicine investigational therapeutics that aim to improve the seizure burden and neurodevelopmental outcomes in patients with CNKSR2 EAS/ID.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age between 6 and 21 years (inclusive) at time of consent.
- •Confirmed CNKSR2 mutation, as demonstrated by genetic testing and confirmed by the investigators.
- •Confirmed intellectual disability or developmental delays, as defined by the American Academy of Pediatrics (Moeschler, J, et al. 2014).
Exclusion Criteria
- •Known pathogenic or clinically suspected mutation in a seizure-associated gene besides CNKSR
- •Confirmed mutation in a gene besides CNKSR2 that is known to increase the severity of the seizure phenotype.
- •Known central nervous system structural abnormality confirmed by imaging scan of the brain that is not consistent with the clinical phenotype of CNKSR2 EAS / ID.
Outcomes
Primary Outcomes
Change from baseline in resting state background brain activity during sleep as measured by phase lag index using electroencephalography (EEG).
Time Frame: Baseline, Month 12, Month 24
Phase lag index ranges between 0 and 1 and is unitless. A phase lag index of zero indicates either no coupling or coupling with a phase difference centered around 0 mod π.
Change from baseline in functional connectivity within the language network using resting-state functional magnetic resonance imaging (fMRI).
Time Frame: Baseline, Month 12, Month 24
Functional connectivity is unitless.
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) scaled scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in functional connectivity within the epileptiform network using resting-state functional magnetic resonance imaging (fMRI).
Time Frame: Baseline, Month 12, Month 24
Functional connectivity is unitless.
Change from baseline in cortical evoked response to self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Time Frame: Baseline, Month 12, Month 24
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in resting state brain activity as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Time Frame: Baseline, Month 12, Month 24
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in neurodevelopmental status as measured by Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) scaled scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 1, maximum score: 19).
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) V-Scale Scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 1, maximum score: 24).
Change from baseline in performance on the Receptive One-Word Picture Vocabulary Test, 4th Edition standard scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: \< 55, maximum score: \> 165).
Change from baseline in ADHD Rating Scale, 4th Edition (ADHD-RS-IV) inattention subscale raw scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Change in physical functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change in social functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change from baseline in cortical evoked response to altered auditory feedback during self-produced speech as measured by voxel-wise source reconstructed brain activation using magnetoencephalography (MEG).
Time Frame: Baseline, Month 12, Month 24
Voxel-wise source reconstructed brain activation assesses localized brain function by mapping neural activity at the voxel level. It is a unitless measure.
Change from baseline in spike-wave index during sleep as measured by percentage using electroencephalography (EEG).
Time Frame: Baseline, Month 12, Month 24
Spike-wave index is the sum of all spike and slow wave minutes multiplied by 100 and divided by the total non-rapid eye movement sleep minutes.
Change from baseline in neurodevelopmental status as measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) standard scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 45, maximum score: 155).
Change from baseline in neurodevelopmental status as measured by the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition (WPPSI-IV) composite scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) T-scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 20, maximum score: 80).
Change from baseline in performance on the Expressive One-Word Picture Vocabulary Test, 4th Edition standard scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: \< 55, maximum score: \> 165).
Change in emotional functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).
Change from baseline in neurodevelopmental status as measured by the Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) composite scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 40, maximum score: 160).
Change from baseline in neurodevelopmental status as measured by Parent Report Form of Vineland Adaptive Behavior Scales, 3rd Edition (Vineland-3) Adaptive Behavior Composite score and Domain scores.
Time Frame: Baseline, Month 12, Month 24
Higher scores indicate a better outcome (minimum score: 20, maximum score: 140).
Change in hyperactivity as measured by ADHD Rating Scale, 4th Edition (ADHD-RS-IV) hyperactivity subscale raw scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 9).
Change in school functioning as measured by Pediatric Quality of Life Inventory (PedsQL) scale scores.
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
Lower scores indicate a better outcome (minimum score: 0, maximum score: 100).