Journal of Neurology

, Volume 261, Issue 5, pp 983–991 | Cite as

Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature

  • Wolfgang Nachbauer
  • Michael Nocker
  • Elfriede Karner
  • Iva Stankovic
  • Iris Unterberger
  • Andreas Eigentler
  • Rainer Schneider
  • Werner Poewe
  • Margarete Delazer
  • Sylvia Boesch
Original Communication


Episodic ataxia type 2 (EA2) is an autosomal dominant inherited neurological disorder that is characterized by paroxysmal episodes of ataxia. The causative gene for EA2 is CACNA1A which codes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel (Cav2.1). We detected a novel point mutation in the CACNA1A gene in a large Austrian family. All ten affected family members harbored a heterozygous c.3089+2T>C nucleotide exchange in intron 19. In silico modeling demonstrated a loss of the splice site of exon 19 by the mutation, which most likely results in exon skipping without frameshifting or use of an alternative splice site. Clinically, the family exhibited frequent ataxic episodes accompanied by headache in some individuals, which showed a good treatment response to acetazolamide or aminopyridine. Interictal phenotype variability was high ranging from an unremarkable clinical examination to a progressive cerebellar syndrome. Detailed cognitive testing with standardized neuropsychological tests revealed specific deficits in various domains including memory, executive functions and visual abilities. Moreover, a striking coincidence of socio-phobic behavior and anxiety disorders was detected within this family, which interfered with activities of daily living and has to be taken in consideration in EA2 patient management. We here characterize the phenotype of this novel CACNA1A mutation, review the respective literature and discuss implications on diagnosis and patient management.


Episodic ataxia CACNA1A Clinical phenotype Cognition 



The authors would like to acknowledge Andreas Janecke for his advice and support in genetic counselling.

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

415_2014_7310_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 22 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Wolfgang Nachbauer
    • 1
  • Michael Nocker
    • 1
  • Elfriede Karner
    • 1
  • Iva Stankovic
    • 2
  • Iris Unterberger
    • 1
  • Andreas Eigentler
    • 1
  • Rainer Schneider
    • 3
  • Werner Poewe
    • 1
  • Margarete Delazer
    • 1
  • Sylvia Boesch
    • 1
  1. 1.Department of NeurologyMedical University InnsbruckInnsbruckAustria
  2. 2.Department of NeurologyUniversity of BelgradeBelgradeSerbia
  3. 3.Department of BiochemistryLeopold-Franzens-University InnsbruckInnsbruckAustria

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