Spinocerebellar ataxias – genotype-phenotype correlations in 104 Brazilian families

Abstract

OBJECTIVE:Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias.METHODS:We studied 150 patients from 104 families with spinocerebellar ataxias who had received molecular genetic testing for spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17, and dentatorubral-pallidoluysian atrophy. A statistical analysis of the results was performed using basic descriptive statistics and the correlation coefficient (r), Student's t-test, chi-square test, and Yates' correction. The statistical significance level was established for p-values <0.05.RESULTS:The results show that the most common subtype was spinocerebellar ataxia 3, which was followed by spinocerebellar ataxia 10. Moreover, the comparison between patients with spinocerebellar ataxia 3, spinocerebellar ataxia 10, and other types of spinocerebellar ataxia revealed distinct clinical features for each type. In patients with spinocerebellar ataxia 3, the phenotype was highly pleomorphic, although the most common signs of disease included cerebellar ataxia (CA), ophthalmoplegia, diplopia, eyelid retraction, facial fasciculation, pyramidal signs, and peripheral neuropathy. In patients with spinocerebellar ataxia 10, the phenotype was also rather distinct and consisted of pure cerebellar ataxia and abnormal saccadic eye movement as well as ocular dysmetria. Patients with spinocerebellar ataxias 2 and 7 presented highly suggestive features of cerebellar ataxia, including slow saccadic ocular movements and areflexia in spinocerebellar ataxia 2 and visual loss in spinocerebellar ataxia 7.CONCLUSIONS:Spinocerebellar ataxia 3 was the most common subtype examined, followed by spinocerebellar ataxia 10. Patients with spinocerebellar ataxia 2 and 7 demonstrated highly suggestive features, whereas the phenotype of spinocerebellar ataxia 3 patients was highly pleomorphic and spinocerebellar ataxia 10 patients exhibited pure cerebellar ataxia. Epilepsy was absent in all of the patients with spinocerebellar ataxia 10 in this series.

Itajaí, Santa Catarina – Azorean ancestry and spinocerebellar ataxia type 3

“…They include autosomal dominant cerebellar ataxias, or spinocerebellar ataxias (SCAs), which are characterized by progressive degeneration of the cerebellum and its afferent and efferent connections 1,2 . Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is the most common autosomal dominant cerebellar ataxia worldwide and is particularly common in Brazil 1,2,3 . The first description of MJD was by Coutinho and Andrade in 1978, who studied 40 patients in 15 families from the Azores 4 .…”

“…A new genetic disorder with an autosomal dominant pattern involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions was defined. 4 In the late 1980s, the eponym Machado-Joseph disease was suggested, but the disease subsequently became universally known as SCA3 1,2,3 . The condition shows remarkable clinical heterogeneity, reflecting the underlying genetic defect, an unstable CAG trinucleotide repeat expansion in the SCA3 gene that varies in size among affected patients.…”

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

“…SCA3 is an autosomal dominant, multisystem, neurodegenerative disorder that presents with significant phenotypical variability, even within the same family 15,22 . In the series presented here, the subphenotype most commonly found was type 2, which is the classic form described in the literature 23 .…”

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

“…Machado-Joseph disease, also known as spinocerebellar ataxia type 3 (SCA3), is currently considered the most common form of SCA worldwide. Among SCA, the relative frequency of SCA3 in Brazil is about 69-92% 2,3 . SCA3 is a multisystem neurodegenerative disorder involving predominantly the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems.…”