A comprehensive clinical and genetic study of a large Mexican population with spinocerebellar ataxia type 7

Abstract

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration. We recently described one of the largest series of patients with SCA7 that originated from a founder effect in a Mexican population, which allowed us to perform herein the first comprehensive clinical, neurophysiological, and genetic characterization of Mexican patients with SCA7. In this study, 50 patients, categorized into adult or early phenotype, were clinically assessed using standard neurological exams and genotyped using fluorescent PCR and capillary electrophoresis. Patients with SCA7 exhibited the classical phenotype of the disease characterized by cerebellar ataxia and visual loss; however, we reported, for the first time, frontal-executive disorders and altered sensory-motor peripheral neuropathy in these patients. Semiquantitative analysis of ataxia-associated symptoms was performed using Scale for the Assessment and Rating of Ataxia (SARA) and the Brief Ataxia Rating Scale (BARS) scores, while extracerebellar features were measured employing the Inventory of Non-ataxia Symptoms (INAS) scale. Ataxia rating scales confirmed the critical role size of cytosine-adenine-guanine (CAG) repeat size on age at onset and disease severity, while analysis of CAG repeat instability showed that paternal rather than maternal transmission led to greater instability.

Motor and cognitive impairments in spinocerebellar ataxia type 7 and its correlations with cortical volumes

“…Our results in SCA7 are supported by previous studies in verbal memory and fluency performance described in other SCAs (including SCA1, SCA2, SCA3, and SCA6), which deficits where underpinned by executive dysfunctions (Bürk et al., , , ; Le Pira et al., ; Maruff et al., ; Suenaga et al., ). In addition, our results are in accordance with the impaired frontal‐executive screening previously described in SCA7 (Velázquez‐Pérez et al., ), suggesting a pervasive executive dysfunction in different types of SCAs.…”

“…However, performance on the MMSE was significantly lower in SCA7 than controls, which may imply signs of neuropsychological deficits not detected by the clinical cut‐off points of the MMSE, but recognized through fronto‐executive screening test (Velázquez‐Pérez et al., ), or during the evaluation of specific components in extensive neuropsychological tests (Vaca‐Palomares et al., ).…”

“…A transverse and longitudinal study with three patients mentioned the possibility of cognitive deficits in this disease (Moriarty et al., ; Sokolovsky, Cook, Hunt, Giunti, & Cipolotti, ). A study that included a more representative sample of patients also described executive dysfunctions in SCA7 patients, but its cognitive evaluation was restricted to a frontal‐executive screening test in which SCA7 patients showed lower global scores compared to controls (Velázquez‐Pérez et al., ). Although more information is needed to develop a complete characterization of the integrity of the different cognitive domains in SCA7, it should be noted that the neural bases of the cognitive impairments are even less explored.…”

Spinocerebellar ataxia: relationship between phenotype and genotype – a review

“…SCA7 is caused by CAG triplet repeat expansions in ATXN7. A higher CAG repeat number is associated with an earlier AAO, more severe symptoms, rapid clinical progression and a high frequency of diseased vision (85,86). The expansion was highly unstable during transmission, and anticipation was clear.…”

Brief Ataxia Rating Scale: A Reliable Tool to Rate Ataxia in a Short Timeframe

“…However, BARS inter-rater reliability and validity have been demonstrated in other studies with SARA or ICARS totaling 146 patients (50 with SCA7, 44 children with brain tumor, and 52 healthy children). [5][6][7] BARS has also been used as the sole scale in few other studies so far, totaling 176 patients (17 with Niemann-Pick, 12 with SCA2, and 148 with multiple sclerosis). [8][9][10] We recommend BARS for use in clinical practice as a reliable tool to evaluate ataxia effectively and rapidly.…”