Genetic Heterogeneity, Movement Disorders, and White Matter Abnormalities in Pediatric Developmental and Epileptic Encephalopathies: A Retrospective Cohort Study From a National Neurodegenerative and Leukodystrophy Registry Publisher Pubmed



Mohammadi P ; Tehrani S F ; Badv R S ; Pak N ; Ashrafi M R ; Heidari M ; Mohammadi M ; Zamani G ; Rezaei Z ; Nikbakht S ; Movahedinia M ; Babaei M ; Garshasbi M ; Ganji M Show All Authors
Source: Epilepsy Research Published:2026

Abstract

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders characterized by early-onset seizures, developmental impairment, and heterogeneous neurological features. We retrospectively analyzed 37 children meeting strict DEE criteria from the Iranian Neurodegenerative and Leukodystrophy Registry (2016–2024), focusing on movement disorders and white matter (WM) abnormalities. Seizure onset occurred within the first year in 81% (30/37). Movement disorders were observed in 24.3% (9/37), including dystonia, myoclonus, ataxia, chorea, tremor, and oculomotor apraxia, with patterns observed across different genetic etiologies. WM abnormalities were present in 43.2% (16/37), predominantly demyelinating, with gene-associated imaging patterns observed in metabolic/lysosomal genes (CLN6, MFSD8, ITPA) and in variants involving TNK2, SLC13A5, and PIGU. Pathogenic or likely pathogenic variants were identified in 78.4% (29/37), including 18 novel variants across 23 genes, with predominance of loss-of-function variants (72.4%). Within the limitations of this cohort, recognition of combined movement and WM features may support improved diagnostic evaluation and prioritization of genetic testing, particularly in settings with variable EEG findings. These observations warrant validation in larger cohorts to further clarify genotype–phenotype relationships in DEEs. © 2026 Elsevier B.V.