A Comprehensive Review of Spinocerebellar Ataxia Type 2 in Cuba

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia characterized by a progressive cerebellar syndrome associated to saccadic slowing, peripheral neuropathy, cognitive disorders, and other multisystem features. SCA2 is caused by the abnormal expansion of cytosine-adenine-guanine triplet repeats in the encoding region of the ATXN2 gene and therefore the expression of toxic polyglutamine expansions in the ataxin 2 protein, which cause progressive neuronal death of Purkinje cells in the cerebellum and several pontine, mesencephalic, and thalamic neurons among other cells. Worldwide, SCA2 is the second most frequent type of spinocerebellar ataxia, only surpassed by SCA3. Nevertheless, in Holguin, Cuba, the disease reaches the highest prevalence, resulting from a putative foundational effect. This review discusses the most important advances in the genotypical and phenotypical studies of SCA2, highlighting the comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and presymptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities. These findings provide guidelines, from a Cuban viewpoint, for the clinical management of the disease, its diagnosis, genetic counseling, and therapeutical options through rehabilitative therapy and/or pharmacological options.

Impact of disease duration on functional status of patients with spinocerebellar ataxia type 2

“…Cerebellar degeneration in individuals with SCA2 can therefore affect postural control. It has also been suggested that postural instability is one of the main signs of SCA2 and leads to balance deficits and, consequently, limitations on the individual's ability to perform activities of daily living 17 . The ability to maintain balance is an integral part of gross motor skills, and poor balance and inadequate posture result in difficulties performing activities of daily living 18 .…”

The Multiple Faces of Spinocerebellar Ataxia type 2

“…Overt dystonia and marked cognitive impairment are present in a minority of patients. Bulbar and autonomic signs correlate with the disease duration, pyramidal signs with the CAG size, while the cerebellar features and peripheral neuropathy with both 8, 22, 36, 37…”

Couples at risk for spinocerebellar ataxia type 2: the Cuban prenatal diagnosis experience

“…If we consider that mean age for the onset of the disease is 33 years (Velázquez et al 2011), it is possible that many affected patients had gotten descendants before the PND was available. Though, it could also be the result of the reduction in their fitness once the cerebellar syndrome begun.…”

“…It is an adult-onset neurodegenerative condition mainly characterized by a progressive cerebellar syndrome (ataxic gait, cerebellar dysarthria, dysmethria, and dysdiadochokinesia) associated with saccadic slowing, peripheral neuropathy, and cognitive disorders (Velázquez et al 2009(Velázquez et al , 2011Magaña et al 2013).…”