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17-06-2024 | Spinocerebellar Ataxia | Original Communication

Spinocerebellar ataxia 27B: a frequent and slowly progressive autosomal-dominant cerebellar ataxia—experience from an Italian cohort

Authors: Sara Satolli, Salvatore Rossi, Elisa Vegezzi, David Pellerin, Maria Laura Manca, Melissa Barghigiani, Carla Battisti, Giusi Bilancieri, Giorgia Bruno, Elena Capacci, Carlo Casali, Roberto Ceravolo, Sirio Cocozza, Stefano Cotti Piccinelli, Chiara Criscuolo, Matt C. Danzi, Rosa De Micco, Giuseppe De Michele, Marie-Josée Dicaire, Grazia Maria Igea Falcone, Roberto Fancellu, Yasmine Ferchichi, Camilla Ferrari, Alessandro Filla, Nicola Fini, Alessandra Govoni, Filomena Lo Vecchio, Alessandro Malandrini, Andrea Mignarri, Olimpia Musumeci, Claudia Nesti, Sabina Pappatà, Maria Teresa Pellecchia, Alessia Perna, Antonio Petrucci, Maria Grazia Pomponi, Roberta Ravenni, Ivana Ricca, Alessandra Rufa, Elisabetta Tabolacci, Alessandra Tessa, Alessandro Tessitore, Stephan Zuchner, Gabriella Silvestri, Andrea Cortese, Bernard Brais, Filippo M. Santorelli

Published in: Journal of Neurology

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Abstract

Background

Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia.

Objective

Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies.

Methods

We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases.

Results

In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment.

Conclusion

Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.
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Metadata
Title
Spinocerebellar ataxia 27B: a frequent and slowly progressive autosomal-dominant cerebellar ataxia—experience from an Italian cohort
Authors
Sara Satolli
Salvatore Rossi
Elisa Vegezzi
David Pellerin
Maria Laura Manca
Melissa Barghigiani
Carla Battisti
Giusi Bilancieri
Giorgia Bruno
Elena Capacci
Carlo Casali
Roberto Ceravolo
Sirio Cocozza
Stefano Cotti Piccinelli
Chiara Criscuolo
Matt C. Danzi
Rosa De Micco
Giuseppe De Michele
Marie-Josée Dicaire
Grazia Maria Igea Falcone
Roberto Fancellu
Yasmine Ferchichi
Camilla Ferrari
Alessandro Filla
Nicola Fini
Alessandra Govoni
Filomena Lo Vecchio
Alessandro Malandrini
Andrea Mignarri
Olimpia Musumeci
Claudia Nesti
Sabina Pappatà
Maria Teresa Pellecchia
Alessia Perna
Antonio Petrucci
Maria Grazia Pomponi
Roberta Ravenni
Ivana Ricca
Alessandra Rufa
Elisabetta Tabolacci
Alessandra Tessa
Alessandro Tessitore
Stephan Zuchner
Gabriella Silvestri
Andrea Cortese
Bernard Brais
Filippo M. Santorelli
Publication date
17-06-2024
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-024-12506-x