The expanding spectrum of movement disorders in genetic epilepsies

Abstract

An ever‐increasing number of neurogenetic conditions presenting with both epilepsy and atypical movements are now recognized. These disorders within the ‘genetic epilepsy‐dyskinesia’ spectrum are clinically and genetically heterogeneous. Increased clinical awareness is therefore necessary for a rational diagnostic approach. Furthermore, careful interpretation of genetic results is key to establishing the correct diagnosis and initiating disease‐specific management strategies in a timely fashion. In this review we describe the spectrum of movement disorders associated with genetically determined epilepsies. We also propose diagnostic strategies and putative pathogenic mechanisms causing these complex syndromes associated with both seizures and atypical motor control. What this paper adds Implicated genes encode proteins with very diverse functions. Pathophysiological mechanisms by which epilepsy and movement disorder phenotypes manifest are often not clear. Early diagnosis of treatable disorders is essential and next generation sequencing may be required.

Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review

“…Although more than 100 genes have been associated with complex monogenic neurologic disorders featuring pediatric-onset DE/EE and MD [61][62][63], this association has been less investigated in newborns. As a result, the number of reviewed studies is low and, for 70% of genes, only single papers were available.…”

Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue

“…We further found that both male and female Adcy5 –/– mice were characterized by significantly lower voluntary running wheel activity in metabolic chambers. As mutations in the Atp1a3 gene are known to be related to dyskinesia, epilepsies and Parkinson’s disease [ 43 ] this could be a relevant finding in the context of other reports describing a connection between the loss of Adcy5 and movement disorders like dyskinesia or autism-like behavior [ 44 , 45 , 46 ]. Furthermore, we cannot exclude that lower activity in our Adcy5 –/– mice was caused by previously reported movement disorders and contributed to the phenotype differences compared to previous Adcy5 –/– models [ 11 , 13 , 24 ].…”

Early-Onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features

“…Second, genetic heterogeneity is also commonly observed in electroclinical syndromes, when different genes can produce one phenotype. Ohtahara syndrome is an example of genetic heterogeneity with several causative mutated genes already described, including STXBP1, 15 SCN2A, 16 ARX, 17 CASK, 18 GNAO1. 19 When to consider genetic testing Genetic discoveries have enhanced our ability to diagnose developmental and epileptic encephalopathies in clinical practice.…”