Episodic ataxia (EA) syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. EA type 2 (EA2), the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel, and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibl...

OBJECTIVES To characterize the nature of CACNA1A mutation in a previously unreported family with episodic ataxia type 2 (EA2) and to better delineate EA2 clinical features. BACKGROUND Episodic ataxia type 2 is an autosomal dominant disorder characterized by the recurrence of acetazolamide-responsive spells of cerebellar ataxia, usually starting during childhood or adolescence. The mutated gen...

Zhenyu Gao,1 Boyan Todorov,2 Curtis F. Barrett,2,3 Stijn van Dorp,4 Michel D. Ferrari,3 Arn M.J.M. van den Maagdenberg,2,3 Chris I. De Zeeuw,1,4 and Freek E. Hoebeek1 1Department of Neuroscience, Erasmus Medical Centre, 3000 CA Rotterdam, Netherlands; 2Department of Human Genetics, and 3Department of Neurology, Leiden University Medical Centre, 2300 RC Leiden, Netherlands; 4Netherlands Institut...

OBJECTIVE Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder characterized by intermittent ataxia, nausea, vomiting, dysarthria, or nystagmus. We report a case of EA2, which downward gaze palsy exists as a common sign in all her attacks. Responsiveness of EA2 to acetazolamide was observed in this patient.

Heejeong Jeong, M.D.*, Hee Jae Huh, M.D.*, Jinyoung Youn, M.D., Ji Sun Kim, M.D., Jin Whan Cho, Ph.D., and Chang-Seok Ki, M.D. Department of Neurology, Gyeongsang National University School of Medicine, Jinju; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology, Samsung Medical Center, Sungkyunkwan Un...

Episodic ataxia type-2 (EA2) is an inherited movement disorder caused by mutations in the gene encoding the Ca(v)2.1alpha1 subunit of the P/Q-type voltage-gated calcium channel that result in an overall reduction in the P/Q-type calcium current. A consequence of these mutations is loss of precision of pacemaking in cerebellar Purkinje cells. This diminished precision reduces the information enc...

OBJECTIVE Episodic ataxia type 1 (EA1) is a monogenic channelopathy caused by mutations of the potassium channel gene KCNA1. Affected individuals carrying the same mutation can exhibit considerable variability in the severity of ataxia, neuromyotonia, and other associated features. We investigated the phenotypic heterogeneity of EA1 in 2 sets of identical twins to determine the contribution of ...

Ion channel dysfunction causes a range of neurological disorders by altering transmembrane ion fluxes, neuronal or muscle excitability, and neurotransmitter release. Genetic neuronal channelopathies affecting peripheral axons provide a unique opportunity to examine the impact of dysfunction of a single channel subtype in detail in vivo. Episodic ataxia type 2 is caused by mutations in CACNA1A, ...