title: Progressive cerebellar ataxia with variable episodic symptoms--phenotypic diversity of R1668W CACNA1A mutation.
abstract: 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.
authors.affiliation: Department of Neurology, Zürich University Hospital, Zurich, Switzerland. sarah.marti@usz.ch
authors.forename: Sarah
authors.initials: S
authors.lastname: Marti
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baloh
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Jen
authors.forename: Dominik
authors.initials: D
authors.lastname: Straumann
authors.forename: Hans H
authors.initials: HH
authors.lastname: Jung
mesh_terms: 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
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type