Late onset hereditary episodic ataxia.
OBJECTIVE
Episodic ataxias (EA) are hereditary paroxysmal neurological diseases with considerable clinical and genetic heterogeneity. So far seven loci have been reported and four different genes have been identified. Analysis of additional sporadic or familial cases is needed to better delineate the clinical and genetic spectrum of EA.


METHODS
A two generation French family with late onset episodic ataxia was examined. All consenting family members had a brain MRI with volumetric analysis of the cerebellum. Haplotype analysis was performed for the EA2 locus (19p13), the EA5 locus (2q22), the EA6 locus (5p13) and the EA7 locus (19q13). Mutation screening was performed for all exons of CACNA1A (EA2), EAAT1 (EA6) and the coding sequence of KCNA1 (EA1).


RESULTS
Four family members had episodic ataxia with onset between 48 and 56 years of age but with heterogeneity in the severity and duration of symptoms. The two most severely affected had daily attacks of EA with a slowly progressive and disabling permanent cerebellar ataxia and a poor response to acetazolamide. Brain MRI showed in three affected members a decrease in the ratio of cerebellar volume:total intracranial volume, indicating cerebellar atrophy. No deleterious mutation was found in CACNA1A, SCA6, EAAT1 or KCNA1. In addition, the EA5 locus was excluded.


CONCLUSIONS
A new phenotype of episodic ataxia has been described, characterised clinically by a late onset and progressive permanent cerebellar signs, and genetically by exclusion of the genes so far identified in EA.
Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Neurologie, Paris, France.
M
M
Damak
F
F
Riant
M
M
Boukobza
E
E
Tournier-Lasserve
M-G
MG
Bousser
K
K
Vahedi
D000086:Acetazolamide / Q000627:therapeutic use; D017668:Age of Onset; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology; D015220:Calcium Channels / Q000235:genetics; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use; D005091:Exons / Q000235:genetics; D005260:Female; D020234:Gait Ataxia / Q000235:genetics / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree
C107598:CACNB4 protein, human; D015220:Calcium Channels; D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide