Although several theories are implicated in the origin of epilepsy, its cause is still unknown in about 50% of cases. To associate a gene with epilepsy for the first time, families with multiple affected members are needed. The aim of our study is carrying out a clinical-genetic study of multiplex families from Republic of Moldova, for estimating the genetic biomarkers and establishing their weight in epileptogenesis, for further elaboration of a family risk prediction score. In order to achieve the set objective, an epidemiological, descriptive study (2018-2023) started with lancing a National Epilepsy Registry for multiplex families – families with at least 2 relatives of 1st degree with definite epilepsy of unknown aetiology, presumed genetic. The first 10 families were submitted to Whole Exome Sequencing (WES). Our National Epilepsy Registry consists now of 74 families including 186 members. We noted a negative trend of cases of epilepsy with advancing age and an overall prevalence of female subjects. The seizure onset, based on the available EEGs, was mostly focal, and the seizure type – mostly motor. The awareness during the seizures, in the majority of the affected subjects – was impaired. The first WES results showed that the most involved chromosomes in Moldovan probands, with potentially epileptogenic variants are the pairs 4, 7, 10, 12, 15 and 17. We also underlined the mostly affected genes: AUTS2, KCNMA1, SUFU, CHL1, MYH1, EDC3, LIAS, TBCD and ATXN1 genes. From all the detected variants, 24% were classified as deleterious and probably pathogenic, 45% were tolerated according to SIFT and 8% were benign or of unknown significance (VUS) according to Polyphen. The rest 22% were VUS according to both predictors. The familial segregation induced the “bottle neck” effect (the families’ cases remain unresolved), demonstrating the role of the trio sequencing in increasing the WES accuracy. Subjects continue to be recruited and included in the National Register of epilepsy of unknown aetiology, presumed genetic. The register is constantly being updated.