Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy.
OBJECTIVE: This review article focuses on clinical and genetic features of paroxysmal neurological disorders featuring episodic ataxia (EA) and epilepsy and help clinicians recognize, diagnose, and treat patients with co-existing EA and epilepsy. It also provides an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.
METHODS: Based on a literature review on Pubmed database, a list of genes linked to paroxysmal neurological disorders featuring EA and epilepsy were compiled. Online Mendelian Inheritance in Man (OMIM) was used to identify further reports relevant to each gene.
RESULTS: Among the various forms of EAs, only EA1 (KCNA1), EA2 (CACNA1A), EA5 (CACNB4), EA6 (SLC1A3), and EA9 (SCN2A) phenotypes with associated epilepsy have been described. Next-generation sequencing (NGS) has helped in the identification of other genes (e.g.: KCNA2, ATP1A3, SLC2A1, PRRT2) which have shown an overlapping phenotype with EA and epilepsy.
CONCLUSION: Overlapping clinical features between EA and epilepsy may hinder an accurate classification, and complex genotype-phenotype correlation may often lead to misdiagnosis. NGS has increased the awareness of common genetic etiologies for these conditions. In the future, extensive genetic and phenotypic characterizations can help us to elucidate the boundaries of a wide phenotypic spectrum. These insights may help develop new precision therapies in paroxysmal neurological disorders featuring EA and epilepsy.
Eur J Med Genet
Ataxia; Epilepsy; Genetic Association Studies; Humans; Mutation; Phenotype; Sodium-Potassium-Exchanging ATPase
Epilepsy; Episodic ataxia; Paroxysmal neurological disorders
Amadori E, Pellino G, Bansal L, et al. Genetic paroxysmal neurological disorders featuring episodic ataxia and epilepsy. Eur J Med Genet. 2022;65(4):104450. doi:10.1016/j.ejmg.2022.104450