Primary episodic ataxias: diagnosis, pathogenesis and treatment.
Primary episodic ataxias are autosomal dominant channelopathies that manifest as attacks of imbalance and incoordination. Mutations in two genes, KCNA1 and CACNA1A, cause the best characterized and account for the majority of identified cases of episodic ataxia. We summarize current knowledge of clinical and genetic diagnosis, genotype-phenotype correlations, pathophysiology and treatment of episodic ataxia syndromes. We focus on unresolved issues including phenotypic and genetic heterogeneity, lessons from animal models and technological advancement, rationale and feasibility of various treatment strategies, and shared mechanisms underlying episodic ataxia and other far more prevalent paroxysmal conditions such as epilepsy and migraine.
Jen
J C
JC
Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA. jjen@ucla.edu
Graves
T D
TD
Hess
E J
EJ
Hanna
M G
MG
Griggs
R C
RC
Baloh
R W
RW
D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D002524:Cerebellar Ataxia / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics; D051379:Mice; D009154:Mutation; D010641:Phenotype; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D051662:Kv1.1 Potassium Channel; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C496946:KCNA1 protein, human