Abstract
The term Episodic Ataxias (EA) was originally used for a few autosomal dominant diseases, characterized by attacks of cerebellar dysfunction of variable duration and frequency, often accompanied by other ictal and interictal signs. The original group subsequently grew to include other very rare EAs, frequently reported in single families, for some of which no responsible gene was found. The clinical spectrum of these diseases has been enormously amplified over time. In addition, episodes of ataxia have been described as phenotypic variants in the context of several different disorders. The whole group is somewhat confused, since a strong evidence linking the mutation to a given phenotype has not always been established. In this review we will collect and examine all instances of ataxia episodes reported so far, emphasizing those for which the pathophysiology and the clinical spectrum is best defined.
Highlights
Episodic Ataxias (EA) are a genetically heterogeneous group of autosomal dominant disorders characterized by attacks of movement incoordination of variable duration and frequency, often accompanied by additional ictal and interictal symptoms
For only two of them, Episodic Ataxia 5 (EA5) and Episodic Ataxia 6 (EA6), the mutated gene is known, while for the others no responsible gene has been identified, except for Episodic Ataxia 8 (EA8) possibly associated with two candidate genes
Episodic Ataxia 1 (EA1) and Episodic Ataxia 2 (EA2) (Table 1) are due to mutations of the pore alpha subunit of an ion voltage-gated channel: Kv1.1 coded by KCNA1 and Cav2.1 by CACNA1A gene respectively
Summary
Episodic Ataxias (EA) are a genetically heterogeneous group of autosomal dominant disorders characterized by attacks of movement incoordination (cerebellar ataxia) of variable duration and frequency, often accompanied by additional ictal and interictal symptoms. The two most frequent types are EA1 and 2, respectively produced by mutations of genes altering the function of Kv1.1 and Cav 2.1 ion channel Both diseases have a wide spectrum of clinical manifestations. Mutations of the CACNA1A gene, coding for the alpha subunit of Cav 2.1 channels, are the cause of two other allelic disorders, Spinocerebellar ataxia 6 (SCA6) and Familial Hemiplegic Migraine 1 (FHM1). These have features that can overlap with those of EA2. EAs, should be distinguished from other genetic disorders in which episodes of ataxia are not the main clinical feature, but just a possible phenotypic variant. We will describe the whole panorama of EAs, emphasizing those for which the pathophysiology and the clinical spectrum is best defined
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