Molecular Genetic Mechanisms of Infantile Epilepsies and the Impact of Genetic Diagnosis

Molecular Genetic Mechanisms of Infantile Epilepsies and the Impact of Genetic Diagnosis: Gene-Shortening Time of Evaluation in Pediatric Epilepsy Services (Gene-STEPS)

The goal of this study is to discover new genetic causes of infantile epilepsies and evaluate the impact of these discoveries on infants with epilepsy and their families.

Study Overview

• Status: Recruiting
• Conditions: Neonatal Epilepsy; Infantile Epilepsy
• Intervention / Treatment: Genetic: Genomic Sequencing

Detailed Description

Infantile epilepsies are common, affecting 1 in 1000 infants, and are associated with significant morbidity, mortality, healthcare costs, and caregiver burden. Although most infantile epilepsies are believed to have genetic causes, most infants with epilepsy remain genetically "unsolved" and the full genetic landscape of infantile epilepsies is unknown, which limits our ability to develop precision therapies and ultimately improve outcomes for this vulnerable population. This study aims to discover new genetic causes of infantile epilepsies and evaluate the impact of these discoveries on infants with epilepsy and their families, contributing to knowledge that will inform our scientific understanding of normal and abnormal brain development and guide clinical care and implementation of precision medicine for infants with epilepsy.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Beth R Sheidley, MS; Phone Number: 8572185533; Email: beth.sheidley@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Beth R Sheidley, MS; Phone Number: 8572185533; Email: beth.sheidley@childrens.harvard.edu
      • Principal Investigator: Alissa M D'Gama, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Infant Criteria

Inclusion Criteria:

• Seizure onset at less than 12 months of age
• Enrollment within 6 weeks of seizure-related presentation
• Patient at Boston Children's Hospital

Exclusion Criteria:

• Simple febrile seizures
• Acute provoked seizures (e.g., due to sepsis, hemorrhage, electrolyte abnormality, cerebral infarction, hypoxic ischemic encephalopathy, non-accidental injury)
• Genetic or acquired cause of epilepsy already identified, including brain magnetic resonance imaging findings consistent with a specific genetic etiology (e.g., tuberous sclerosis complex)
• Deceased prior to enrollment

Parent Criteria Inclusion Criteria - Parent of eligible infant (see above)

Exclusion Criteria

- Not the legal guardian of the eligible infant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Genomic Sequencing; All enrolled infants receive the intervention (genomic sequencing, including rapid genome sequencing). Comprehensive genomic analyses will be performed to identify genetic diagnoses. Genetic results will be returned to families and infants will be followed until 2.5 years old to evaluate the impact of genetic diagnosis using quantitative validated outcome measures and qualitative parent interviews.

Genetic: Genomic Sequencing; Genomic sequencing data will be comprehensively analyzed for pathogenic variants that explain the participants epilepsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Yield	The diagnostic yield of genomic sequencing will be calculated as the percentage of enrolled infants with epilepsy who receive a genetic diagnosis.	Collected after return of genetic results approximately 2 weeks after infant is enrolled
Short-term clinical utility of genetic testing	The short-term clinical utility of genetic testing will be evaluated using the validated C-GUIDE measure. The C-GUIDE total score will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.	Collected after return of genetic results approximately 2 weeks after infant is enrolled
Parent-perceived (personal) utility of genetic testing	The parent-perceived utility of genetic testing will be evaluated using the validated GENE-U measure. The GENE-U total score will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.	Collected when infant is 2.5 years old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developmental progress	Developmental progress will be evaluated using the Bayley Scales of Infant and Toddler Development Fourth Edition. The cognitive, language, and motor subscale scores will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.	Collected when infant is 2.5 years old
Seizure frequency	The seizure frequency will be evaluated using the seizure frequency outcome measure developed by the American Academy of Neurology and dichotomized as decrease vs no decrease between the two timepoints. The percentage of infants with this outcome will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.	Collected at return of genetic results approximately 2 weeks after infant is enrolled and when infant is 2.5 years old
Parental experiences with genetic testing	This outcome will be evaluated using a qualitative approach. Semi-structured interviews will be performed with a subset of parents using purposive sampling and will be analyzed using a grounded theory iterative approach.	Collected when infant is 2.5 years old

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Alissa M D'Gama, MD, PhD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2021
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 21, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: 1K23NS140397 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No