DEE, MEF2C
Conditions
Keywords
MEF2C Haploinsufficiency Syndrome (MCHS), Developmental and Epileptic Encephalopathy
Brief summary
Phase 0 non-interventional longitudinal study of children and adults with Developmental and Epileptic Encephalopathy (DEE) due to a genetic cause. There are six arms of the study. Arms 1, 2, and 3 are devoted to one example DEE, MEF2C Haploinsufficiency Syndrome (MCHS). Arms 4, 5, and 6 are open to all DEE. Arm 1 (in-person) will enroll children 0 to 15, who will make in-person visits to Weill Cornell Medicine four times over two years. Arm 2 (virtual) will enroll people of all ages and older who will make virtual visits over Weill Cornell Zoom to Weill Cornell Medicine over two years (2 if 16 and older; 4 if 0 to 15). Arm 3 (registry) will enroll people of all ages in an online-only survey. Arms 4 - 6 mirror this structure but they are open to all children with DEE. Arm 4 (in-person) will enroll children of any age, who will make in-person visits every 6 months for 10 years. Arm 5 (virtual) will enroll children of any age for virtual visits, twice a year of 0 to 15, once a year if 16 or older. Arm 6 (registry) will enroll people of all ages in an online only survey.
Interventions
OTHERObservation
This intervention is observation only.
Sponsors
Weill Medical College of Cornell University
Rare Bird Foundation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Molecular diagnosis of a genetic disorder associated with DEE, as confirmed by the study investigators * A neurological phenotype such as epilepsy or developmental delay as confirmed by the study investigators. * English Speaking (Arms 1, 2, 4, 5). The registries may be completed by people who speak any language. ARM 1 (In person cohort) * MEF2C * Age 0 to 15 at the time of study enrollment. * Willingness to travel to New York City four times over two years ARM 2 (Virtual cohort) * MEF2C * Any age at the time of study enrollment * Sufficient internet connectivity to support video teleconferencing * Commitment to fill out all survey instruments ARM 3 (Registry) * MEF2C * Any age at the time of study enrollment * Commitment to fill out one on-line instrument ARM 4 (In person cohort) * Any DEE * Any age at the time of study enrollment * Willingness to travel to New York City four times over two years ARM 5 (Virtual cohort) * Any DEE * Any age at the time of study enrollment * Sufficient internet connectivity to support video teleconferencing * Commitment to fill out all survey instruments ARM 6 (Registry) * Any DEE * Any age at the time of study enrollment * Commitment to fill out one on-line instrument
Exclusion criteria
* Presence of a significant non-DEE-related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the study * History of prematurity (defined as gestational age \<35 weeks), interventricular hemorrhage, structural brain deficit, or congenital heart disease * Presence of a clinical comorbidity deemed by the investigator to potentially confound the typical presentation of DEE
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bayley Scales of Infant and Toddler Development (Fourth Edition) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | Bayley-4 is a standardized assessment tool designed to evaluate children from age 1 month to 42 months. Bayley-4 assesses multiple areas of development, including cognitive, language, motor, social/emotional, and adaptive behavior. It is considered a gold standard by clinicians and researchers. In clinical studies of developmental disorders, Bayley-4 can be used in children older than 42 months. We track scores using the "age equivalent" metric, which runs from 0 month to 42 months in each subdomain. We will explicitly track five domains: cognition, expressive language, receptive language, gross motor, and fine motor. This will result in 5 separate metrics for age equivalency. |
| Change in Observer-Reported Communication Ability (ORCA) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The ORCA is a battery of 84 questions to assess communication ability in children with neurodevelopmental disorders. Seventy items ask about observable behaviors within 22 concepts that cover expressive, receptive and pragmatic areas of communication. Fourteen additional items capture information about the individual's unique ways of communicating, including the modalities the individual uses, their current vocabulary, and aspects of language complexity (e.g. how many words/symbols/gestures are used to communicate a single message). The ORCA measure currently produces a single score that is an estimate of an individual's overall level of communication ability. Higher ORCA T-scores reflect greater communication ability; the mastery of expressive, receptive, and pragmatic types of communication and higher vocabularies for verbal words and symbols on assistive devices. The ORCA T-score range is from 25.8 to 83.8. |
| Change in Peabody Developmental Motor Scales 3 (PDMS-3) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | PDMS-3 is a standardized assessment tool used to measure the motor skills of young children from birth through 5 years of age. As with the Bayley-4, in studies of developmental disorders, the PDMS-3 is regularly used in children older than 5. We will track the age equivalent values in the five subdomains (body control, body transport, object control, hand manipulation, and eye-hand co-ordination). We track the "age equivalent" scores which range from 0 to 71 months in each subdomain. This will result in 5 "age equivalent" scores for each participant -- one for each subdomain. |
| Change in Pediatric Epilepsy Learning Healthcare System (PELHS) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | Dr. Grinspan (PI) designed the PELHS questions to characterize children with epilepsy for clinical care and research. These questions will be supplemented by standardized historical questions to understand the timing of critical events, such as the age of the first seizure, key EEG findings, and therapeutic trials. PELHS includes categorical items. Examples of categorical items include epilepsy syndrome and epilepsy type. |
| Change in QI-Disability | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | QI-Disability is a quality-of-life instrument specifically designed for children with intellectual disabilities with a strong track record of use in developmental and epileptic encephalopathies like CDKL5 disorder. Some core domains include physical, psychological, social, functional well-being, and self-determination. Each item is rated on a 5-point Likert scale and item scores are scaled to range from 0 to 100 with higher scores indicating better quality of life. |
| Change in Children's Sleep Habits Questionnaire (CSHQ) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | CHSQ is a parent survey focusing on bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night awakenings, and parasomnias. The scores range from 33 (no sleep disturbances) to 99 (profound sleep disturbances). Scores of 41 or higher indicate clinically significant sleep disturbance. We will analyze this variable as a binary variable (\< 41 vs \>= 41). |
| Change in Childhood Autism Rating Scale-2 (CARS-2) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The CARS-2 is a diagnostic tool used to assess the severity of the autism spectrum disorder in children as young as 2. It consists of 15 items, each of which is rated on a scale from 1-4 (i.e. total score ranges from 15 to 60). Scores from 15-29.5 reflect minimal-to-no symptoms of autism spectrum disorder, scores from 30-36.5 reflect mild-to-moderate symptoms of autism spectrum disorder, and scores from 37-60 reflect severe symptoms of autism spectrum disorder. We will analyze these data as an ordinal categorical variable (four levels). |
| Change in Vineland Adaptive Behavior Scales (Third Edition) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The Vineland Scales are a standard assessment of development for all ages. We will focus on five domains. For the adaptive behavior score, we will use the standard score -- the range is from 20 (lowest) to 140 (highest). For gross motor and fine motor domains, we will track the age equivalent value (range from 0 months to 83 months). For receptive and expressive language, we will also track the age equivalent value (range from 0 months to 252 months). There will be a total of four age equivalent values per participant (one for each domain). |
| Change in Communication Function Classification System (CFCS) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | CFCS is a single-item, five-level scale to assess communication abilities, originally designed for people with cerebral palsy. It describes the ability of individuals to send and receive information with familiar and unfamiliar communication partners. A level 5 score represents least effective communication, while a level 1 score represents most effective communication. |
| Change in Alberta Infant Motor Scale (AIMS) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The AIMS is a standardized assessment tool used to evaluate the motor development of infants from birth to 18 months of age, focusing on gross motor skills, consisting of 58 items. The lowest possible score is 0 and the highest possible score is 58. We will provide interpretation by estimating the age-equivalent based on the 50%ile age associated with each score based on the normative percentile curves provided with the AIMS assessment worksheets -- for example a score of 3 is roughly equivalent to 0 months and a score of 50 is roughly equivalent to 11 months. |
| Change in Gross Motor Function Measure-88 (GMFM-88) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The GMFM-88 is a standardized clinical tool to evaluate changes in gross motor function in children aged 5 months and up. The scores range from 0-100, with a higher score indicating higher gross motor function. |
| Change in Gross Motor Function Classification System (GMFCS) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | GMFCS is a single-item, five-level scale to assess motor function, originally designed for people with cerebral palsy. It focuses on the degree of support required to maneuver in the environment. Scores range from I (least impaired) to V (most impaired). |
| Change in Manual Ability Classification System (MACS) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | MACS is a single-item, five-level scale to describe manual (hand and arm) abilities, initially designed for people with cerebral palsy. It measures how well children can handle objects, focusing on speed, accuracy, and requirements for support. The scores range from I (least impaired) to V (most impaired). |
| Change in WHO Motor Milestones | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The WHO Motor Development Milestones are part of a standardized framework developed through the WHO Multicenter Growth Reference Study. These milestones focus on six key gross motor skills: sitting without support, standing with assistance, hands-and-knees crawling, walking with assistance, standing alone, and walking alone. Rather than a numbered score, these motor milestones are given "windows of achievement" for the following ages: Sitting without support: 3.8 to 9.2 months Standing with assistance: 4.8 to 11.4 months Hands-and-knees crawling: 5.2 to 13.5 months Walking with assistance: 5.9 to 13.7 months Standing alone: 6.9 to 16.9 months Walking alone: 8.2 to 17.6 months |
| Change in Seizure Diaries | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The seizure diaries are caregiver-maintained records of a participant's seizure count and frequency. Each round of diary collection will provide a number of seizures per six weeks. We will track this quantitatively as "seizures per week". |
| Change in Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | PELHS-QOL-2 is a brief, validated, 2-question assessment of quality of life for children with epilepsy. It can be scored from 0 (no impact of seizures or medication side effects on usual routines) to 8 (daily impact of seizures and side effects on usual routines). |
| Change in Pediatric Sleep Questionnaire (PSQ) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The PSQ evaluates sleep-related breathing disorders, snoring, and daytime sleepiness in children. The PSQ has a score range from 0 to 1, with a higher score indicating a higher likelihood for sleep-related breathing disorders. |
| Change in Aberrant Behavior Checklist (ABC) | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The ABC is a validated scale to measure psychiatric symptoms and behavioral disturbance in children with intellectual disabilities. The lowest possible score of 0 indicates no aberrant behaviors. The highest possible score is 174. Higher scores indicate a higher degree of aberrant behavior. |
| Change in Mullen Scales of Early Learning | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | Information about cognitive functioning is generated in four distinct areas (visual reception, fine motor, receptive language, and expressive language scales). There also is a measure of gross motor skills.The Mullen Scales provides a composite score. The lowest possible raw score in each subsection is a 5, for a lowest possible overall score of 25. The highest possible composite score is 218. |
| Change in (DAYC-2) Developmental Assessment of Young Children, Second Edition | at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years | The DAYC-2 is a popular test used to identify children birth through 5-11 with possible delays in the following domains: cognition, communication, social-emotional development, physical development, and adaptive behavior. The domains can be assessed independently, so examiners may test only the domains that interest them or test all five domains when a measure of general development is desired. The lowest possible raw score is 0, while the highest possible raw score is 253. |
Countries
United States
Contacts
CONTACTZachary Grinspan, MD MS
CONTACTNatalie Wayland, BS
PRINCIPAL_INVESTIGATORZachary Grinspan, MD MS
Weill Medical College of Cornell University
Outcome results
None listed