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

Trial Summary

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 data supports the effectiveness of the treatment Genomic Sequencing for Infantile Epilepsy?

Genomic sequencing, including techniques like Whole Genome Sequencing and Whole Exome Sequencing, has been shown to improve the diagnosis of epilepsy by identifying genetic causes, which can lead to more personalized and effective treatment plans. Studies have demonstrated that these methods can provide a genetic diagnosis for up to 30% of early-onset epilepsy cases, helping to tailor treatments to individual needs and potentially improving outcomes. ^{1 2 3 4 5}

Is genomic sequencing safe for humans?

The research does not provide specific safety data for genomic sequencing, but it is generally used as a diagnostic tool to help understand and treat conditions like epilepsy. It can sometimes reveal unexpected information, which may require careful handling by healthcare providers. ^{1 3 4 6 7}

How is genomic sequencing different from other treatments for infantile epilepsy?

Genomic sequencing is unique because it helps identify the genetic causes of epilepsy, allowing for a more personalized treatment approach. Unlike traditional treatments that may not address the underlying genetic factors, this method can lead to more accurate diagnoses and targeted therapies. ^{1 2 3 5 8}

What is the purpose of this trial?

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.

Research Team

Alissa M D'Gama, MD, PhD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing. [2019]

5. England pubmed.ncbi.nlm.nih.gov

From next-generation sequencing to targeted treatment of non-acquired epilepsies. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical utility of exome sequencing in a pediatric epilepsy cohort. [2023]

7. England 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Determining the best candidates for next-generation sequencing-based gene panel for evaluation of early-onset epilepsy. [2021]