Genomic Sequencing for Infantile Epilepsy

Overseen By Beth R Sheidley, MS

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Simple febrile seizures, Acute provoked seizures, Genetic or acquired cause, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the genetic causes of seizures in infants to better understand their epilepsy. By using genomic sequencing, researchers aim to identify genetic factors that could explain why these seizures occur. The findings could improve care for infants and provide useful information to their families. Infants under 12 months old who have had their first seizure and are seen at Boston Children's Hospital might be suitable for this study. As an unphased study, this trial offers families the chance to contribute to groundbreaking research that could lead to better understanding and treatment of infant epilepsy.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What prior data suggests that genomic sequencing is safe for infants with epilepsy?

Research has shown that genetic testing is generally safe for infants and children with epilepsy. Studies have found that quick genetic tests provide important medical insights without causing harm. For instance, one study discovered that using these tests in children with severe epilepsy helped doctors make better treatment choices, with no negative effects on the children. Another study confirmed the feasibility of using rapid genetic testing in infants with new epilepsy, suggesting it is safe enough for regular care. Overall, genetic testing for epilepsy appears to be a safe process that offers valuable information for managing the condition. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about genomic sequencing for infantile epilepsy because it offers a personalized approach to diagnosis and treatment. Unlike traditional methods that rely on symptom management or broad-spectrum medications, genomic sequencing dives into the infant's DNA to pinpoint the exact genetic causes of epilepsy. This can lead to quicker, more accurate diagnoses and potentially tailor treatments to the individual needs of the child, improving outcomes and quality of life. Additionally, the rapid genomic sequencing used in this approach provides families with answers much faster than conventional genetic testing, which can be crucial during the early, critical stages of a child's development.

What evidence suggests that genomic sequencing is effective for infantile epilepsy?

Research has shown that genomic sequencing is a powerful tool for identifying the genetic causes of infant epilepsy. Studies have found that this method can pinpoint a genetic cause in up to 50% of severe epilepsy cases. The success rate is high, particularly with advanced sequencing techniques. In this trial, all enrolled infants will undergo genomic sequencing, including rapid genome sequencing, to identify genetic diagnoses. Rapid genetic testing has improved diagnosis and significantly aided in treatment decisions. Understanding the genetic basis of epilepsy through genomic sequencing can lead to more targeted treatments and better outcomes for infants. ^{6 7 8 9 10}

Who Is on the Research Team?

Alissa M D'Gama, MD, PhD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for infants with epilepsy who had their first seizure before turning one year old and are patients at Boston Children's Hospital. Their legal guardians must enroll them within six weeks of the initial seizure-related visit. Infants with simple febrile seizures, known genetic causes of epilepsy, or certain acute provoked seizures cannot participate.

Inclusion Criteria

Patient at Boston Children's Hospital

I am the parent of a child who meets the study criteria.

My seizures started before I was 1 year old.

Exclusion Criteria

I have had brief fever-related seizures.

Not the legal guardian of the eligible infant

Deceased prior to enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic Sequencing

All enrolled infants receive genomic sequencing, including rapid genome sequencing. Comprehensive genomic analyses will be performed to identify genetic diagnoses.

2 weeks

1 visit (in-person)

Follow-up

Infants are followed until 2.5 years old to evaluate the impact of genetic diagnosis using quantitative validated outcome measures and qualitative parent interviews.

2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Genomic Sequencing

Trial Overview The study aims to identify new genetic factors causing infantile epilepsies using genomic sequencing and assess how these findings affect the affected infants and their families.

How Is the Trial Designed?

Group I: Genomic Sequencing Experimental Treatment 1 Intervention

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.

Genomic Sequencing is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Genomic Sequencing for:

• Diagnostic testing for genetic disorders in prenatal diagnosis
• Identification of genetic causes of fetal anomalies

Approved in European Union as Genomic Sequencing for:

• Prenatal diagnosis of genetic disorders
• Investigation of fetal anomalies

Approved in Canada as Genomic Sequencing for:

• Prenatal diagnostic testing for genetic conditions
• Evaluation of fetal anomalies

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

In a study of 116 children with epilepsy onset before 2 years of age, 54% were diagnosed with an epilepsy syndrome, and 65% had a known etiology, highlighting the potential for effective diagnosis in early onset epilepsy.

Next-generation sequencing (WES/WGS) was performed in 22% of cases and provided a diagnostic yield of 58%, suggesting it is a valuable tool for identifying genetic causes in children with epilepsy, particularly in complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study. Stödberg, T., Tomson, T., Barbaro, M., et al.[2021]

Exome sequencing (ES) significantly impacts clinical decision-making in pediatric epilepsy, leading to provider recommendations in 41.5% of families, which included changes in medication and referrals to specialists.

The study highlights the importance of ES in improving patient care by providing anticipatory guidance and access to resources, supporting its implementation as a routine diagnostic tool for children with unexplained epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of exome sequencing in a pediatric epilepsy cohort. Graifman, JL., Lippa, NC., Mulhern, MS., et al.[2023]

Next-generation sequencing (NGS) identified genetic causes in 34.5% of 116 patients with early-onset epilepsy, highlighting its effectiveness as a diagnostic tool.

The study found that patients with earlier seizure onset and a family history of epilepsy were more likely to have identifiable disease-causing variants, suggesting targeted genetic testing can improve diagnosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the best candidates for next-generation sequencing-based gene panel for evaluation of early-onset epilepsy. Lee, J., Lee, C., Ki, CS., et al.[2021]

Next-generation sequencing (NGS) has significantly improved the diagnosis of epilepsy, providing genetic diagnoses for up to 30% of patients with early-onset epilepsy, which helps in understanding the disease mechanisms and phenotypic variability.

About 25% of epilepsy patients with de novo mutations have identifiable genetic targets that can guide personalized treatment strategies, highlighting the potential of NGS in precision medicine for epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From next-generation sequencing to targeted treatment of non-acquired epilepsies. Møller, RS., Hammer, TB., Rubboli, G., et al.[2020]

In a study of 277 children with epilepsy, targeted gene panel sequencing revealed a diagnostic yield of 23.1%, with a higher yield of 28.9% in patients with developmental delay, highlighting the importance of genetic testing in timely diagnosis.

The identification of pathogenic variants in younger patients suggests that early genetic testing can lead to better treatment strategies and avoid unnecessary procedures, emphasizing the need for prompt genomic diagnostics in pediatric epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice. Blazekovic, A., Gotovac Jercic, K., Meglaj, S., et al.[2022]

In a study of 190 pediatric patients with epilepsy of unknown cause, larger customized gene panels (>25 kb) yielded a significantly higher diagnostic rate of pathogenic variants (29%) compared to smaller panels (<25 kb) which had a rate of 13%.

For patients with non-developmental and epileptic encephalopathy (non-DEE), larger panels were more effective, while smaller panels (up to 10 genes) were sufficient for those with developmental and epileptic encephalopathy (DEE), indicating that panel size should be tailored based on the patient's condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters. Willimsky, EK., Munzig, A., Mayer, K., et al.[2021]

Whole Genome Sequencing (WGS) has the potential to provide earlier and more accurate diagnoses for children with pharmacoresistant epilepsy, which could significantly improve treatment outcomes.

Parents of children with epilepsy expressed a strong desire for WGS results, believing they could help manage their child's condition, but also faced concerns about the implications of sharing unexpected genetic information with family members.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing. Jaitovich Groisman, I., Hurlimann, T., Godard, B.[2019]

A survey of 204 neurologists revealed that 59% believe Whole Genome Sequencing (WGS) results should only be shared if they have clear clinical utility, while 41% support sharing results that may not have direct clinical relevance but could influence patient decisions, such as reproductive choices.

Most neurologists (75%) feel responsible for recontacting patients about newly discovered mutations related to their medical condition, and over half (53.5%) believe they should inform patients about clinically significant incidental findings, highlighting the need for professional guidelines that address these ethical considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring neurologists' perspectives on the return of next generation sequencing results to their patients: a needed step in the development of guidelines. Hurlimann, T., Jaitovich Groisman, I., Godard, B.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11790612/

Diagnostic efficiency of exome-based sequencing in pediatric ... NGS is an effective method for uncovering the genetic foundations of pediatric epilepsy, with diagnostic yields varying based on the sequencing approach used.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525505025002938

A crash course in genomics for epilepsy clinicians In severe epilepsies, whole exome or whole genome sequencing can identify a genetic diagnosis in up to 50% of cases. Although the therapeutic impact of most ...

3. nature.com nature.com/articles/s41431-025-01870-5

Impact of rapid genomic testing on clinical outcomes ... This study demonstrates high diagnostic yield and significant therapeutic benefit from rapid genetic testing in patients with epilepsy.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18403

Clinical whole genome sequencing in pediatric epilepsy ... Whole exome sequencing (WES) and whole genome sequencing (WGS) have revolutionized the capacity to detect rare monogenic causes of epilepsy, ...

5. frontiersin.org frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00020/full

Next Generation Sequencing Methods for Diagnosis of ... Here, we review these commonly used NGS techniques to determine their suitability for application to epilepsy genetic diagnostic testing.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479891/

Impact of rapid genomic testing on clinical outcomes ... Conclusion: this study demonstrates high diagnostic yield and significant therapeutic benefit from rapid genetic testing in patients with ...

7. nature.com nature.com/articles/s41431-025-01870-5.pdf

Impact of rapid genomic testing on clinical outcomes of ... In this study, we therefore evaluate the therapeutic benefits of rapid genetic testing in children with severe epilepsy. Methods: the clinical ...

8. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(23)00246-6/fulltext

Evaluation of the feasibility, diagnostic yield, and clinical ... Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy.

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.17534

Clinical utility of exome sequencing in a pediatric epilepsy ... This study systematically reviewed the impact of ES results on clinical decision-making and patient care in a pediatric epilepsy cohort at a tertiary care ...

10. epilepsy.com epilepsy.com/causes/genetic/testing

Genetic Testing for Epilepsy This genetic test involves analysis of the entire DNA code or “genome” to look for DNA changes or “variants” in genes associated with epilepsy.