Clinical and Genetic Evaluation of Spinocerebellar Ataxia Type 10 in 16 Brazilian Families.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder in which patients have a slowly progressive cerebellar ataxia, with dysarthria, dysphagia, and epilepsy. The aims of this study were to characterize the phenotypic expression of SCA10 and to examine its genotype-phenotype relationships. Ninety-one Brazilian patients with SCA10 from 16 families were selected. Clinical and epidemiological data were assessed by a standardized protocol, and severity of disease was measured by the Scale for the Assessment and Rating of Ataxia (SARA). The mean age of onset of symptoms was 34.8 ± 9.4 years. Sixty-two (68.2%) patients presented exclusively with pure cerebellar ataxia. Only 6 (6.6%) of the patients presented with epilepsy. Patients with epilepsy had a mean age of onset of symptoms lower than that of patients without epilepsy (23.5 ± 15.5 years vs 35.4 ± 8.7 years, p = 0.021, respectively). All cases of intention tremor were in women from one family. This family also had the lowest mean age of onset of symptoms, and a higher percentage of SCA10 cases in women. There was a positive correlation between duration of disease and severity of ataxia (rho = 0.272, p = 0.016), as quantified by SARA. We did not find a statistically significant correlation between age of onset of symptoms and expansion size (r = - 0.163, p = 0.185). The most common clinical presentation of SCA10 was pure cerebellar ataxia. Our data suggest that patients with epilepsy may have a lower age of onset of symptoms than those who do not have epilepsy. These findings and the description of a family with intention tremor in women with earlier onset of symptoms draw further attention to the phenotypic variability of SCA10.

Spinocerebellar ataxias in Southern Brazil: Genotypic and phenotypic evaluation of 213 families.

OBJECTIVES: To describe and correlate the genotype and phenotype of patients diagnosed with SCAs in southern of Brazil. PATIENTS AND METHODS: Data were collected from the records of our ataxia outpatient clinic. We included 460 patients from 213 families, who were divided into four groups: SCA3, SCA10, Other SCAs and Undetermined. RESULTS: The most frequent type was SCA3 (45.7%), followed by SCA10 (18.3%), SCA2 (6.5%), SCA1 (4.3%), SCA7 (1.8%), and SCA6 (0.65%). The Undetermined group represented 22.8% of all patients. We observed a high frequency of SCA10 when compared to data from other studies, which can be explained by a founder effect in our region. Statistically significant differences were found for several symptoms when comparing SCA groups, especially lid retraction (p < 0.001), ophthalmoplegia (p < 0.001), visual loss (p < 0.001) and slow saccades (p < 0.001) which may help clinically differentiate SCAs and allow neurologists to request the right confirmatory genetic test and define prognosis. Also, the prevalence of epilepsy in SCA10 patients was lower than usual (4.8%), suggesting a genetic variation of the disease. CONCLUSION: Although SCA3 remains the most common, we observed a high frequency of SCA10 in our region. In addition, some symptoms and signs might help differentiate the SCAs.

Analysis of CAG repeats in five SCA loci in Mexican population: epidemiological evidence of a SCA7 founder effect.

Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders. CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the causative genes have been identified as the cause of different SCA. In this study, we simultaneously genotyped SCA1, SCA2, SCA3, SCA6, and SCA7 applying a fluorescent multiplex polymerase chain reaction assay. We analyzed 10 families with SCA (64 patients) from five different communities of Veracruz, a Mexican southeastern state, and identified 55 patients for SCA7 and 9 for SCA2, but none for SCA1, SCA3, or SCA6. To our knowledge, this sample represents one of the largest series of SCA7 cases reported worldwide. Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles.

Spinocerebellar ataxia type 6 in Brazil / Ataxia espinocerebelar tipo 6 no Brasil

Spinocerebellar ataxia type 6 (SCA 6) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansion in the SCA6 gene, a alpha 1A voltage-dependent calcium channel subunit gene on chromosome 19p13. SCA-6 is characterized predominantly by slowly progressive pure cerebellar ataxia with late onset. We report three index patients, with pure, late onset, cerebellar ataxia, belonging to three different Brazilian families, all of them with Japanese ancestry, from Hokkaido island of Japan.

Ataxia espinocerebelar tipo 6 (AEC6) é uma ataxia cerebelar autossômica dominante causada por uma expansão repetida do tripleto CAG no gene da AEC, que é uma sub-unidade do canal de cálcio voltagem-dependente alfa1A localizada no cromossomo 19p13. A AEC6 é caracterizada predominantemente por quadro de ataxia cerebelar pura, com início tardio, e evolução lentamente progressiva. Relatamos três pacientes índices, com ataxia cerebelar pura, de início tardio, pertencentes a três diferentes famílias brasileiras, todas com ancestrais japoneses, oriundas da ilha de Hokkaido.

Ataxia espinocerebelosa 7: Investigación clínica y genética en una familia argentina / Spinocerebellar ataxia 7: Clinical and genetic investigation in an Argentine family

Las ataxias espino cerebelosas (AEC), constituyen un grupo de trastornos hereditarios neurodegenerativos de herencia autosómica dominante. Se caracterizan principalmente por la presencia clínica de ataxia cerebelosa asociada a oftalmoplejía, disartria, signos piramidales o extrapiramidales y pérdida de la sensibilidad profunda. La AEC 7 pertenece al grupo de las ataxias espinocerebelosas en la cual el trastorno es consecuencia de la expansión del triplete CAG localizado en el cromosoma 3 p12-p21. La característica clínica de dicha ataxia es la pérdida de la agudeza visual y posterior ceguera. Presentamos tres individuos de una familia con ataxia cerebelosa, pérdida de la agudeza visual y otros signos neurológicos. El diagnóstico fue confirmado por medio del análisis genético en el cual se observó la anormalidad característica de la AEC 7. Este es el primer caso de AEC 7 en Argentina confirmado por estudio genético. En la revisión de la literatura (hasta enero 2006) se hallaron sólo dos familias notificadas en América Latina. El objetivo del trabajo es el de enfocar la atención en el diagnóstico de esta enfermedad degenerativa en pacientes que se presentan con ataxia cerebelosa progresiva asociada con disminución de la agudeza visual e historia familiar positiva.

Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.