Phenotypic and Genotypic Spectrum of Early-Onset Developmental and Epileptic Encephalopathies—Data from a Romanian Cohort

Genes - Tập 13 Số 7 - Trang 1253
Anca‐Lelia Riza1,2, Ioana Streață1,2, Eugenia Roza3,4, Magdalena Budișteanu5,6,7, Catrinel Iliescu6, Carmen Burloiu6, Mihaela-Amelia Dobrescu1,2, Ștefania Dorobanțu1,2, Adina Dragoș1,2, Andra Grigorescu1, Tiberiu Tătaru8, Mihai Ioana1,2, Raluca Ioana Teleanu3,4
1Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
2Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania
3Department of Pediatric Neurology, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania
4Department of Pediatric Neurology, Dr. "Victor Gomoiu" Clinical Children′s Hospital, 022102 Bucharest, Romania
5Department of Genetics, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania
6Department of Pediatric Neurology, Prof. Dr. Alex. Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania
7Medical Genetics Laboratory, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania
8Emergency County Hospital Targu Jiu, 210218 Târgu Jiu, Romania

Tóm tắt

Early-onset developmental epileptic encephalopathy (DEE) refers to an age-specific, diverse group of epilepsy syndromes with electroclinical anomalies that are associated with severe cognitive, behavioral, and developmental impairments. Genetic DEEs have heterogeneous etiologies. This study includes 36 Romanian patients referred to the Regional Centre for Medical Genetics Dolj for genetic testing between 2017 and 2020. The patients had been admitted to and clinically evaluated at Doctor Victor Gomoiu Children’s Hospital and Prof. Dr. Alexandru Obregia Psychiatry Hospital in Bucharest. Panel testing was performed using the Illumina® TruSight™ One “clinical exome” (4811 genes), and the analysis focused on the known genes reported in DEEs and clinical concordance. The overall diagnostic rate was 25% (9/36 cases). Seven cases were diagnosed with Dravet syndrome (likely pathogenic/pathogenic variants in SCN1A) and two with Genetic Epilepsy with Febrile Seizures Plus (SCN1B). For the diagnosed patients, seizure onset was <1 year, and the seizure type was generalized tonic-clonic. Four additional plausible variants of unknown significance in SCN2A, SCN9A, and SLC2A1 correlated with the reported phenotype. Overall, we are reporting seven novel variants. Comprehensive clinical phenotyping is crucial for variant interpretation. Genetic assessment of patients with severe early-onset DEE can be a powerful diagnostic tool for clinicians, with implications for the management and counseling of the patients and their families.

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