Autosomal dominant cerebellar ataxias in Spain: molecular and clinical correlations, prevalence estimation and survival analysis.
BACKGROUND
The genetic and clinical profile of autosomal dominant cerebellar ataxias (ADCA) displays marked geographical and ethnical variability.


METHODS
We have analysed the molecular and clinical correlations in an ethnically homogeneous sample of 30 Spanish ADCA kindreds. Minimal point prevalence for the region of Cantabria was estimated.


RESULTS
Seventy per cent of the families harboured known mutations. Areflexia, slow saccades and hypopallesthesia predominated in SCA2; nystagmus, pyramidal signs or areflexia restricted to the legs in SCA 3; and retinal degeneration, pyramidal signs and slow saccades in SCA 7. Anticipation and intergenerational instability were greater in SCA 7. Length of expansions and age at onset were inversely correlated in all SCA subtypes. Larger expansions correlated with areflexia in SCA 2, with pyramidal signs in SCA 3 and with early visual impairment in SCA 7. Survival was similar among the different SCA subtypes. Prevalence of ADCA in Cantabria was 1.6 cases per 100,000 population.


CONCLUSIONS
This report shows the epidemiological, clinical and genetic profile of ADCA in Spain, providing additional data regarding the broad clinical heterogeneity of these disorders and the variability of the genotype-phenotype correlations.
Infante
J
J
Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria, Santander, Spain. neuro@humv.es
Combarros
O
O
Volpini
V
V
Corral
J
J
Llorca
J
J
Berciano
J
J
D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015835:Ocular Motility Disorders / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D011712:Pyramidal Tracts / Q000503:physiopathology; D012021:Reflex, Abnormal / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D016019:Survival Analysis; D019680:Trinucleotide Repeat Expansion