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The genetic landscape in infantile epilepsies: a molecular–genetic specific diagnosis for therapeutic aspects and outcome

Objective: (1) To investigate the genetic landscape in infantile epilepsies specific with a molecular-genetic specific diagnosis for therapeutic aspects and outcome. Methods: The study group consisted of 150 patients with infantile epilepsy between 2010-2021. The most likely specific etiologies were coded by agreement of two reviewers. Based genetic tests (karyotyping, micro-array, gene panels, clinic exome analysis, and whole-exome sequencing) on patients and whole-exome trio analysis were discussed on the Ege Pediatric Neurogenetic Case-Management Councils. Candidate genetic epilepsies are divided into four subgroups by molecular basis; cell proliferation defect, cell migration defects, inborn errors of metabolism, and lastly loss-of-function variants. Results: Of the 150 patients, 107 (71.3%) had a molecular-genetic diagnosis using next-generation sequencing tests, the remaining had a specific diagnosis with chromosomal tests and multiplex ligation-dependent probe amplification. Three subgroups categorized with the seizure occurrence time; group I; 22 (14.7%) patients with seizures in the neonatal period (<28 days of postnatal life), group II: 34 (22.6%) patients with seizures in the early infantile period (between 1 to 3 months of age, and group II: 94 (62.6%) patients with seizures in the late infantile period (> 3months of age). Specific molecular diagnosis established with the genetic tests; cellular proliferation defect (n:18,12%), cell migration defect (n:6, 4%), metabolic (n:2,1.3%), functional 106 (70.7%). The specific molecular-genetic diagnosis provided a significant therapeutic yield in 76 (50.5%) patients with precision medicine (Table 1). Conclusion: This retrospective cohort study with extensive use of genetic testing in children with infantile epilepsies provided more diagnostic and therapeutic yields.
Keywords: ınfantile epilepsy, neonatal seizure, genetic landscape