Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic
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ORIGINAL ARTICLE
Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic Petya Bogdanova-Mihaylova 1 & Josephine Hebert 1 & Sharon Moran 1 & Michael Murphy 1 & Deirdre Ward 2 & Richard A. Walsh 1,3 & Sinéad M. Murphy 1,3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Establishing a molecular diagnosis in patients with progressive ataxia is often challenging due to significant genetic and clinical heterogeneity and requires a methodical approach with expert clinical evaluation and investigations. We describe the 5-year experience of the National Ataxia Clinic (NAC), Ireland. All adults with ataxia attending the NAC between 2014 and 2019 were evaluated. All individuals underwent detailed clinical assessment and investigations including, where appropriate, genetic testing using nextgeneration sequencing. For all patients, acquired causes were ruled out. A total of 254 patients from 196 families were assessed; with growth of the clinic cohort by 82% from 133 to 242 over the 5-year period. The underlying genetic cause was identified in 128/196 probands (65.3%). The detection rate for repeat expansion disorder gene testing was 47.7% (82/172) and using NGS gene panel, a genetic diagnosis was obtained in 30/84 (35.7%). Whole exome sequencing identified the molecular diagnosis in 4/20 (20%), and whole genome sequencing provided genetic diagnosis in 1/5 (20%). The commonest diagnosis was Friedreich’s ataxia (68/128, 53.1%). SPG7-associated ataxia was the second most common diagnosis (21/128, 16.4%), followed by ANO10-associated spastic ataxia, ataxia telangiectasia (AT), and other rarer phenotypes. Our results highlight that careful clinical phenotyping in a dedicated ataxia clinic is crucial for appropriate genetic testing in selected patients in a timely manner. Advanced genetic testing has significantly improved the diagnostic yield in patients with suspected genetic ataxia and should be considered in all individuals with negative repeat expansion testing. Keywords Cerebellar Ataxia . Ataxia clinic . Genetics . Next-generation sequencing . Whole exome sequencing
Introduction
Petya Bogdanova-Mihaylova and Josephine Hebert are joint first authors Richard A Walsh and Sinéad M Murphy are joint senior authors Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01180-0) contains supplementary material, which is available to authorized users. * Petya Bogdanova-Mihaylova [email protected] 1
National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Dublin 24, Ireland
2
Department of Cardiology, Tallaght University Hospital, Dublin 24, Ireland
3
Academic Unit of Neurology, Trinity College Dublin, Dublin, Ireland
Cerebellar ataxias (CA) are a highly heterogeneous group of rare neurological disorders and, depending on the underlying cause, are broadly divided into two main groups, acquired and genetic. CA can present at any age, traditionally classified as early (< 20 years) or late onse
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