Genetic Diagnosis and Personalized Medicine for Patients With Epilepsy

Study design Non-pharmacological (diagnostic) interventional, single-center, biological, observational, prospective Interventions

• Collection of clinical and instrumental data of patients with epilepsy at first outpatient visit (time 0) and at one-year follow-up: age, gender, education, age of onset of seizures, new diagnosis/check-up, type of seizure according to the ILAE classification, type of epilepsy according to the ILAE classification, frequency of epileptic seizures, etiology, for cases with a genetic/probably genetic etiology application of an ad hoc score to determine the probability of a positive outcome for exome research, neurological objectivity, presence of comorbidities, parameters of EEG background activity, parameters relating to interictal EEG anomalies, parameters relating to critical EEG anomalies, magnetic resonance parameters, therapies used, effectiveness of therapies used, side effects of therapies, duration of therapy, dosages of therapy, neuropsychological and psychological outcome (score on standard tests/questionnaires administered according to age as required by the standard of care), functional outcome expressed with the modified Rankin scale; clinical and instrumental data will also be collected for sick or healthy parents of patients with epilepsy who will be identified for the exome analysis of the trio (proband + parents) during the recruitment phase (not at follow-up), while they will not be collected sensitive data relating to the parents of patients who did not undergo an exome (observational part of the study).
• Qualitative evaluation of the EEG according to the ACNS guidelines and whenever possible through quantitative analysis of the EEG parameters at time 0 and at 1 year follow up. In the quantitative analysis, ad hoc algorithms will be used to extract the temporal and frequency domain characteristics of the EEG traces.
• Sequencing and analysis of the exome of at least 30 patients and their natural parents (plus any other first-degree relatives affected by epilepsy or genetic condition related to epilepsy) for a total of at least 90 exomes.

With the exception of WES sequencing, the other diagnostic-evaluative procedures are part of the normal clinical management of patients.

Genotype-phenotype correlations The WES will be evaluated in relation to the clinical picture on the basis of a close collaboration between clinicians (neurologists), biologists, geneticists, bioinformatics involved in the project. The acquired data will also be used to define the risk of recurrence, prognosis, monitoring of complications and identification of possible targeted treatments.

Inclusion criteria

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.

Inclusion criteria

for exome candidate patients:

• 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.

Exclusion criteria

• 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.