Genetic Diagnosis and Personalized Medicine for Patients With Epilepsy

NCT06321822 | Recruiting

• 1 other identifier: EPIEXOME
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Background Epilepsy is a common neurological disorder. It affects 50 million people worldwide and has the highest incidence in pediatric age. According to the latest classification of the ILAE (International League against Epilepsy), epilepsies are divided into lesional (symptomatic) and non-lesional/genetic forms. Symptomatic causes of epilepsy may include scarring, tumors, strokes, and brain developmental disorders such as dysplasias. In approximately 30% of epilepsies a genetic cause of epilepsy can be hypothesized. Since the identification of the first epilepsy gene in 1995, over the next 25 years over 500 genes associated with epilepsy have been identified. The importance of many genes and many gene variants identified in many genes is not yet clear and the mutations identified in different genes require confirmation with functional studies and confirmation on larger series of patients. Furthermore, the genetic defect underlying many patients with epilepsy remains unknown to this day, despite a high level of gene sequencing effort. Molecular studies on these genes have demonstrated how pathogenic variants on these genes determine a protein dysfunction that can cause neuronal hyperexcitability and pathological synchronization of neuronal networks leading to epileptic seizures and brain dysfunction. A notable complication in the field of epilepsy genetics is represented by the fact that the concept of a gene/a disease is valid only in a few cases, as there is a high phenotypic and genotypic heterogeneity so that a gene can present different types of epilepsy even within the same family. This means that there is a complex multigenic and multifactorial genetic substrate for which the impact of a specific genetic variant is conditioned by variants of other genes. This concept is particularly valid for the most common epileptic forms such as idiopathic generalized epilepsies. The integration of genetic analysis with epileptological characterization in clinical practice is increasingly crucial in defining a clear molecular diagnosis in patients whose disease cause would otherwise remain unknown, and potentially allows avoiding other unnecessary diagnostic investigations. It is therefore expected that this will lead to optimizing clinical management and reducing overall costs over time. The genetic finding can constitute a useful biomarker for defining the outcome of the disease and for guiding clinical decisions such as the best choice of therapy. Despite the advantages, before starting the genetic testing process, patients and their family members should be informed about the ethical issues that may arise from genetic testing, the technical limitations, legal aspects and costs of genetic investigation. Aim of the study Characterization of patients with epilepsy recruited at the Hospital Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan (Italy) and analysis with exome NGS sequencing of patients with the highest probability of genetic diagnosis with exome (use of a probability score) Endpoints of study are the following:

1. 1.Identification of the genetic cause of the forms of genetic epilepsies with the highest probability of molecular diagnosis with exome
2. 2.Clinical-instrumental and epileptological characterization according to the ILAE classification of patients with epilepsy followed at the Fondazione IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico
3. 3.Correlation of clinical and instrumental parameters (in particular EEG and neuropsychological) of epilepsy recorded on the database with etiology, outcome and response to therapy

Conditions

Epilepsy

Keywords

genetics; NGS exome sequencing; Personalized medicine; Genotype-phenotype correlation

Outcome Measures

Primary Outcomes (1)

• Identification of the genetic cause in patients with clinically probable genetic epilepsy using WES

  Identification of the genetic cause of patients with forms of epilepsy with a high probability using of genetic etiology, selected from the cohort of epileptic patients followed at Fondazione IRCCS Ca' Ospedale Maggiore Policlinico, using WES

  1 year after enrollment

Secondary Outcomes (4)

• Clinical and epileptological characterization of patients with epilepsy according to ILAE seizure and epilepsy classification

  1 year after enrollment

• Characterization of qualitative Electroencefagraphy (EEG) features of patients with the different epilepsy types

  1 year after enrollment

• Quantitative EEG (qEEG) characterization of patients with the different epilepsy types

  3 year after enrollment

• Characterization of the clinical and instrumental features of patients with specific genetic etiology

  1 year after enrollment

Study Arms (1)

Epileptic Patients recruited for observational study

EXPERIMENTAL

Patients with epilepsy recruited for observation study. When criteria for genetic epilepsy will be met, they will undergo testing for genetic investigation through exome NGS sequencing

Diagnostic Test: Whole exome sequencing (WES)

Interventions

Whole exome sequencing (WES) DIAGNOSTIC_TEST

Patient selected for genetic study will undergo blood sample collection for DNA estraction, biobank storage and WES study

Epileptic Patients recruited for observational study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Study population: patients with epilepsy.
• Patients who meet all of the following criteria will be included:
• Patients both minors and adults diagnosed with epilepsy;
• of both sexes;
• followed at the pediatric and adult epilepsy and electroencephalography clinics of the U.O.C. Neurophysiopathology - IRCCS Ca' Granda Fondazione Ospedale Maggiore Policlinico;
• Informed consent of the patient if an adult and capable of providing consent independently or of the parents or legal guardians in the case of a minor/individual not capable of providing consent independently.
• Availability of DNA samples from the patient and both natural parents;
• Prediction of high positive genetic diagnosis Patients diagnosed with epilepsy will be recruited among those followed at the pediatric and adult epilepsy and electroencephalography clinics of the U.O.C. Neurophysiopathology - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, after signing the consent.

You may not qualify if:

• Patients who possess at least one of the following criteria will be excluded:
• Patients arriving for evaluation with the initial suspicion of epilepsy who during the diagnostic work-up were found to be suffering from a different pathology;
• Patients who have refused consent to participate in the study.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead

Study Sites (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

MeSH Terms

Conditions

Epilepsy

Interventions

Exome

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Robertino Dilena, MD

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica Massacesi

CONTACT

+390255032982; federica.massacesi@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 20, 2024
• Study Start: August 2, 2021
• Primary Completion: August 2, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)