Warianty liczby kopii genów w spektrum padaczki rozwojowej i padaczki z encefalopatią: seria przypadków z Indonezji

Developmental epilepsy (DE) and developmental and epileptic encephalopathy (DEE) comprise neurodevelopmental disorders in which epilepsy occurs alongside developmental impairment of varying contributions from the underlying etiology and epileptic activity. Advances in genetic testing, including whole-exome sequencing (WES), whole-genome sequencing (WGS), and chromosomal microarray analysis (CMA), have facilitated the identification of copy number variants (CNVs); however, data on CNV-associated epilepsy and neurodevelopmental disorders remain limited in Southeast Asia, including Indonesia. This retrospective case series describes the clinical and genetic characteristics of four Indonesian children across the DE-DEE spectrum with pathogenic CNVs identified at a tertiary referral hospital in Yogyakarta, Indonesia. Among 48 patients who underwent WES, CNVs were identified in five; four underwent further genetic characterization and were included in this case series, while one patient died before additional testing could be performed. Clinical manifestations included early-onset seizures, developmental delay or intellectual impairment, and abnormal EEG and/or neuroimaging findings. Genetic findings included a 2q24.3 deletion involving SCN1A in a patient with Dravet syndrome and 15q11.2-q13.1 deletions involving UBE3A in three patients with clinical features of Angelman syndrome. Confirmatory testing using WGS or CMA further characterized the identified CNVs. This case series expands the clinical and molecular data on pathogenic CNVs associated with pediatric epilepsy and neurodevelopmental disorders in an underrepresented Southeast Asian population and illustrates the complementary roles of sequencing and chromosomal analysis in genetic diagnosis.