Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia

Giordano, Ilaria, Harmuth, Florian, Jacobi, Heike, Paap, Brigitte, Vielhaber, Stefan, Machts, Judith, Schöls, Ludger, Synofzik, Matthis, Sturm, Marc, Tallaksen, Chantal, Wedding, Iselin M., Bösch, Sylvia, Eigentler, Andreas, Warrenburg, Bart van de, Gaalen, Judith van, Kamm, Christoph, Dudesek, Ales, Kang, Jun-Suk, Timmann, Dagmar, Silvestri, Gabriella, Masciullo, Marcella, Klopstock, Thomas, Neuhofer, Christiane, Ganos, Christos, Filla, Alessandro, Bauer, Peter, Montcel, Sophie Tezenas du and Klockgether, Thomas (2017): Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. In: Neurology, Vol. 89, No. 10: pp. 1043-1049

Abstract

Objective: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations. Methods: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing. Results: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94+/-0.74, p<0.0001) and disease duration (0.22+/-0.06 per additional year, p=0.0007) were associated with a higher SARA score. Forty-eight participants who did not fulfill MSA-C criteria and had a disease duration of >10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6+/-6.0 vs 16.0+/-5.8, p=0.0200) and a slower annual SARA increase (1.1+/-2.3 vs 3.3+/-3.2, p=0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made. Conclusions: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0028-3878
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English