Trial Summary
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.
Is Genomic Sequencing a promising treatment for infant epilepsy?Yes, Genomic Sequencing is a promising treatment for infant epilepsy. It helps doctors find the genetic causes of epilepsy, leading to more accurate diagnoses and personalized treatments. This can improve the quality of life for children by providing targeted therapies and avoiding unnecessary tests.34567
What safety data exists for genomic sequencing in infantile epilepsy?The provided research does not directly address safety data for genomic sequencing in infantile epilepsy. The studies focus on the diagnostic utility, clinical impact, and perspectives of parents and neurologists regarding the use of genomic sequencing technologies like Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) in epilepsy. They discuss the potential for earlier and more accurate diagnoses, the impact on clinical decision-making, and the challenges of interpreting incidental findings, but do not specifically mention safety data.12568
What data supports the idea that Genomic Sequencing for Infantile Epilepsy is an effective treatment?The available research shows that Genomic Sequencing, like Whole Genome Sequencing and Whole Exome Sequencing, helps in diagnosing epilepsy more accurately and earlier. This is important because it can lead to more personalized and effective treatments. For example, one study found that targeted gene panels or whole exome sequencing can provide a genetic diagnosis for up to 30% of patients with early-onset epilepsy. Another study showed that children with certain genetic variants had seizures at a younger age, suggesting that early genomic testing can lead to better treatment and avoid unnecessary procedures. Overall, these findings suggest that Genomic Sequencing is a valuable tool in managing infantile epilepsy.23567
Do I need to stop my current medications to join the trial?The trial protocol does not specify whether you need to stop taking your current medications.
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
My seizures started before I was 1 year old.
Exclusion Criteria
I have had brief fever-related seizures.
I have had seizures caused by a specific condition like infection or stroke.
My epilepsy has a known genetic or acquired cause.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Genomic SequencingExperimental Treatment1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Boston Children's HospitalBoston, MA
Loading ...
Who is running the clinical trial?
Boston Children's HospitalLead Sponsor
References
Exploring neurologists' perspectives on the return of next generation sequencing results to their patients: a needed step in the development of guidelines. [2019]The use of Next Generation Sequencing such as Whole Genome Sequencing (WGS) is a promising step towards a better understanding and treatment of neurological diseases. WGS can result into unexpected information (incidental findings, IFs), and information with uncertain clinical significance. In the context of a Genome Canada project on 'Personalized Medicine in the Treatment of Epilepsy', we intended to address these challenges surveying neurologists' opinions about the type of results that should be returned, and their professional responsibility toward recontacting patients regarding new discovered mutations.
Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing. [2019]The use of Next Generation Sequencing technologies (NGS), such as Whole Genome Sequencing (WGS), is expected to improve the often complex and protracted course of treatment of patients with epilepsy by providing an earlier and more accurate diagnosis. As part of the "Personalized medicine in the treatment of epilepsy" project, which aimed to determine whether WGS could be used as a valuable "diagnostic tool" in pharmacoresistant epilepsies, we examined parents' expectations, hopes, and concerns upon receiving results related to their child's epilepsy, comorbidities, resistance to medication, and genetic information on unrelated conditions, and how these results could impact their and their child's life.
From next-generation sequencing to targeted treatment of non-acquired epilepsies. [2020]Within the last decade, next-generation sequencing (NGS) has resulted in remarkable advances in the field of epilepsy genetics. NGS has become a routine part of the diagnostic workup in many countries. A workup that has led to higher diagnostic yields and insights into the underlying disease mechanisms. Areas covered: In this review, we report on the recent contributions of NGS testing to the diagnosis and the understanding of pathophysiological mechanisms, phenotypic variability, and genetic heterogeneity of different epilepsies including developmental and/or epileptic encephalopathies, focal and generalized epilepsies. Furthermore, we discuss how the increased knowledge of the genetic architecture of the epilepsies can be translated into more personalized treatment. Expert opinion/commentary: Targeted gene panels or whole exome sequencing can provide a genetic diagnosis for up to 30% of the patients with early-onset epilepsy. Despite current technical limitations, NGS-based technologies can become the new first-tier diagnostic tests in the epilepsies. As the pool of genetically diagnosed patients has increased, so has the demand for more accurate treatment. Approximately 25% of the epilepsy patients with de novo mutations have genetic diagnoses with potential targets for precision medicine approaches, thus illustrating the enormous utility of genetic testing for therapeutic decision-making.
Determining the best candidates for next-generation sequencing-based gene panel for evaluation of early-onset epilepsy. [2021]Genetic testing is an emerging diagnostic approach in early-onset epilepsy. Identification of the heterogeneous genetic causes of epilepsy may mitigate unnecessary evaluations and allow more accurate diagnosis and therapy. We aimed to uncover genetic causes of early-onset epilepsy using next-generation sequencing (NGS) to elucidate the diagnostic candidates and evaluate the diagnostic yield of targeted gene panel testing.
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]Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis.
Next Generation Sequencing in Pediatric Epilepsy Using Customized Panels: Size Matters. [2021]Next generation sequencing (NGS) with customized gene panels is a helpful tool to identify monogenic epilepsy syndromes. The number of genes tested within a customized panel may vary greatly. The aim of the present study was to compare the diagnostic yield of small (25 kb) customized epilepsy panels.
Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice. [2022]Epilepsy is one of the most common neurological disorders with diverse phenotypic characteristics and high genetic heterogeneity. Epilepsy often occurs in childhood, so timely diagnosis and adequate therapy are crucial for preserving quality of life and unhindered development of a child. Next-generation-sequencing (NGS)-based tools have shown potential in increasing diagnostic yield. The primary objective of this study was to evaluate the impact of genetic testing and to investigate the diagnostic utility of targeted gene panel sequencing. This retrospective cohort study included 277 patients aged 6 months to 17 years undergoing NGS with an epilepsy panel covering 142 genes. Of 118 variants detected, 38 (32.2%) were not described in the literature. We identified 64 pathogenic or likely pathogenic variants with an overall diagnostic yield of 23.1%. We showed a significantly higher diagnostic yield in patients with developmental delay (28.9%). Furthermore, we showed that patients with variants reported as pathogenic presented with seizures at a younger age, which led to the conclusion that such children should be included in genomic diagnostic procedures as soon as possible to achieve a correct diagnosis in a timely manner, potentially leading to better treatment and avoidance of unnecessary procedures. Describing and discovering the genetic background of the disease not only leads to a better understanding of the mechanisms of the disorder but also opens the possibility of more precise and individualized treatment based on stratified medicine.
Clinical utility of exome sequencing in a pediatric epilepsy cohort. [2023]Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. 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 medical center.