The Spectrum of Movement Disorders in Children with Genetic Developmental and Epileptic Encephalopathies: A...

Movement disorders (MDs) often remain underexplored in genetic developmental and epileptic encephalopathies (DEEs), largely due to limited awareness, phenotypic heterogeneity and the considerable burden of drug-resistant epilepsy.

This study aimed to characterize the etiological profile of genetic DEEs with coexisting MDs, delineate the spectrum of MDs and explore associations between movement disorder phenomenology and underlying genetic variants.

A single-center cross-sectional observational study was conducted over 1 year (Jan 2024-Jan 2025) at a tertiary referral center in North India. Children aged 0 to 18 years with genetic DEEs and coexistent MDs were included. Clinical data, including seizure and MD videos, neuroimaging/ EEG findings and genetic reports were analyzed. Ethical approval was obtained from the Institutional Ethics Committee.

Thirty-two children were enrolled (53% being boys) with a median age at enrolment of 4.15 years (IQR: 3-5.1 years). The majority (47%) had infantile/late-infantile-onset DEE, followed by childhood-onset DEE in 37.5%, while only five had early infantile-onset DEE. STXBP1 (9%) was the most frequently affected single gene, while ion channel genes (sodium/potassium) represented the most affected neurobiological pathway (19%). The most prevalent MDs were stereotypies (44%), followed by dystonia (37.5%), ataxia (28%), myoclonus (22%), chorea (16%), tremor (6%) and Parkinsonism (3%); mixed phenomenology was observed in 44%. The majority (84.5%) presented with chronic, persistent MDs, while paroxysmal MDs were observed with ATP1A3, SCN2A, UFC1, GNB1 and GNB5 variants.

Enhancing clinical awareness, accurately characterizing phenomenology and understanding genetic underpinnings are essential for a focused diagnostic approach in these complex overlap syndromes.