Movement Disorders in Developmental and Epileptic Encephalopathies.

BACKGROUND

Monogenic developmental and epileptic encephalopathies (DEE) frequently feature co-occurring movement disorders. Gene discovery has expanded epilepsy-dyskinesia syndromes (EDS) from classic associations such as stereotypies in Rett syndrome to PRRT2-related infantile seizures with paroxysmal dyskinesia and crouched gait in SCN1A-associated Dravet syndrome.

OBJECTIVES

To outline the movement disorders spectrum in EDS, propose a pragmatic syndrome-based clinical framework, group implicated genes into mechanistic categories, highlight selected genotype-phenotype correlations, and summarize symptomatic and precision therapeutic options.

METHODS

A non-systematic, structured literature review identified monogenic disorders reported with EDS, grouping publications into four tiers: multi-etiology cohorts; small series and narrative/systematic reviews; single-gene or pathway-focused reports; and mechanistic/therapeutic studies.

RESULTS

Eight cohort studies and multiple tier 2-3 series and reviews yielded 245 single-gene associations, most mapping to ion channel and synaptic signaling pathways. Across DEE cohorts, movement disorders occurred in roughly one-quarter to over one-half of patients, were often hyperkinetic (notably dystonia and stereotypies), and frequently combined multiple phenomenologies. We grouped clinical presentations into early and late infantile-onset EDS, Rett and Rett-like syndromes, paroxysmal/episodic and relapsing-remitting disorders, disorders with severe acute motor exacerbations, and hypokinetic/progressive phenotypes. Treatments are guided by gene- and mechanism-informed strategies including sodium-channel blockers, glutamatergic modulators, ketogenic diet, agents for paroxysmal dyskinesias, and deep brain stimulation in life-threatening crises.

CONCLUSIONS

Movement disorders are common, often severe, and genetically heterogeneous across EDS. A syndrome-based approach integrating clinical features, neuroimaging, and broad genetic testing (including copy number variants and repeat expansions) can guide symptomatic management and emerging precision therapies.