Progressive cerebellar ataxia with variable episodic symptoms--phenotypic diversity of R1668W CACNA1A mutation.
We describe a family with an R1668W mutation in the CACNA1A gene who presented with a broader clinical spectrum and more variable features than previously reported. The mother had a pure progressive cerebellar ataxia of late onset with downbeat nystagmus, whereas her daughter suffered from episodic ataxia, hemiplegic migraine, and progressive cerebellar ataxia with horizontal gaze-evoked and rebound nystagmus. In both patients, treatment with acetazolamide was ineffective and worsened baseline ataxia, whereas flunarizine ameliorated episodic symptoms. Our report highlights profound phenotypic variability that can be associated with CACNA1A mutations and adds important therapeutic considerations.
Marti
Sarah
S
Department of Neurology, Zürich University Hospital, Zurich, Switzerland. sarah.marti@usz.ch
Baloh
Robert W
RW
Jen
Joanna C
JC
Straumann
Dominik
D
Jung
Hans H
HH
D000328:Adult; D019943:Amino Acid Substitution; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D015220:Calcium Channels / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D009801:Oculomotor Muscles / Q000503:physiopathology; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type