Genetic and metabolic epilepsies in pediatric epilepsy, clinic and diagnostic evaluation

Epilepsy is a common neurological disorder affecting patients of all ages. The etiology of epilepsy constitutes a heterogeneous group of entities. Information on genetic and metabolic etiologies of epilepsy has been increasing along with molecular genetic advancements. This study retrospectively assessed the medical records of children diagnosed with epilepsy, followed up at Hacettepe University, Faculty of Medicine, Department of Pediatric Neurology, between January 2020 and December 2021. Clinical and diagnostic findings for patients with genetic and metabolic epilepsy were further evaluated. Of 972 patients with epilepsy diagnostic codes, 77 were excluded since they did not fulfill the diagnostic criteria for epilepsy. The remaining 895 patients were categorized into etiologic groups: 340 with structural (38%), 99 with genetic (11,1%), 61 with metabolic (6,8%), 21 with infectious (2,3%), 15 with immune (1,7%) and 359 with unknown etiology (40,1%). Genetic epilepsies were divided into subcategories as monogenic disorders detected in 66 patients (67%), copy number variants in 25 patients (25%), and chromosomal disorders in eight patients (8%). SCN1A defect was found in 15 patients and was the most frequent variant in the monogenic disorders group which constituted the major subgroup of genetic epilepsies. Metabolic epilepsies were categorized into subgroups according to their pathophysiological mechanisms: small molecule disorders in 31 patients (50,8%), complex molecule disorders in 15 patients (24,6%), and energy metabolism disorders in 15 patients (24,6%). Early onset seizures, refractory epilepsy, abnormal neurological examination findings, and developmental, cognitive/neuropsychiatric, and medical comorbidities were common features among both genetic and metabolic epilepsies. The mortality rate was highest in the mitochondrial subgroup of metabolic epilepsies. Compared to genetic and metabolic epilepsy series in the literature, variants associated with self-limiting benign epilepsy were relatively rare within our cohort. In genetic epilepsies, the consanguinity rate was similar to the rate of consanguineous marriages in our country, whereas it was higher in metabolic epilepsies. This could be due to the abundance of autosomal recessive inheritance patterns in inborn metabolic disorders.