Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness

NCT07413211 | Recruiting

• 1 other identifier: 24-10028107
• Study Type: observational
• Target: 22,068
• Locations: 1 country
• Sites: 1

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.

Conditions

MEF2C; DEE

Keywords

MEF2C Haploinsufficiency Syndrome (MCHS); Developmental and Epileptic Encephalopathy

Outcome Measures

Primary Outcomes (25)

• Change in Bayley Scales of Infant and Toddler Development (Fourth Edition)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Observer-Reported Communication Ability (ORCA)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Peabody Developmental Motor Scales 3 (PDMS-3)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Pediatric Epilepsy Learning Healthcare System (PELHS)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in QI-Disability

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Children's Sleep Habits Questionnaire (CSHQ)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Childhood Autism Rating Scale-2 (CARS-2)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Vineland Adaptive Behavior Scales (Third Edition)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Communication Function Classification System (CFCS)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Alberta Infant Motor Scale (AIMS)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Gross Motor Function Measure-88 (GMFM-88)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Gross Motor Function Classification System (GMFCS)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Manual Ability Classification System (MACS)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in WHO Motor Milestones

  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

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Seizure Diaries

  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".

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2)

  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).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Pediatric Sleep Questionnaire (PSQ)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Aberrant Behavior Checklist (ABC)

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Seizure Diaries

  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 the percentage of participants who have 50% reduction in seizure frequency at each visit compared to the prior visit.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Mullen Scales of Early Learning

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in (DAYC-2) Developmental Assessment of Young Children, Second Edition

  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.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Children's Sleep Habits Questionnaire (CSHQ)

  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 continuous variable (33 to 99).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Childhood Autism Rating Scale-2 (CARS-2)

  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 a continuous variable (score value).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Pediatric Epilepsy Learning Healthcare System (PELHS)

  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 ordinal items. Examples of ordinal items include seizure frequency (range from "none in the past two years" to "too many to count") and age of epilepsy onset. There is no overall score.

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

• Change in Aberrant Behavior Checklist (ABC)

  The ABC is a validated scale to measure psychiatric symptoms and behavioral disturbance in children with intellectual disabilities. We will track each of five subdomains -- irritability (score range 0 - 45), lethargy (0 - 48), stereotypy (0 - 21), hyperactivity (0 - 48), inappropriate speech (0 -12).

  at baseline, in 6 months, in 1 year, in 1.5 years, and in 2 years

Study Arms (6)

Onsite Cohort with MCHS

This is an in-person cohort of participants with MCHS under age 16 who will meet with investigators at the site location every 6 months for 2 years.

Other: Observation

Virtual Cohort with MCHS

* Has MCHS * Any age at the time of study enrollment * Sufficient internet connectivity to support video teleconferencing * Commitment to fill out all survey instruments

Other: Observation

MCHS Online Registry

* Has MCHS * Any age at the time of study enrollment * Commitment to fill out one on-line instrument

Onsite Cohort with any DEE

* Any DEE * Any age at the time of study enrollment * Willingness to travel to New York City four times over two years

Other: Observation

Virtual Cohort with Any DEE

Any DEE * Any age at the time of study enrollment * Sufficient internet connectivity to support video teleconferencing * Commitment to fill out all survey instruments

Other: Observation

DEE Online Registry

Any DEE * Any age at the time of study enrollment * Commitment to fill out one on-line instrument

Interventions

Observation OTHER

This intervention is observation only.

Onsite Cohort with MCHS; Onsite Cohort with any DEE; Virtual Cohort with Any DEE; Virtual Cohort with MCHS

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

The target population is any individual with a neurological phenotype (developmental delay or seizures) and a known genetic etiology.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Rare Bird Foundation: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

MeSH Terms

Interventions

Observation

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Zachary Grinspan, MD MS

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachary Grinspan, MD MS

CONTACT

(212) 746-3278; zag9005@med.cornell.edu

Natalie Wayland, BS

CONTACT

646-962-3023; naw4006@med.cornell.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: February 26, 2025
• Primary Completion (Estimated): April 30, 2037
• Study Completion (Estimated): April 30, 2037
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)