Objective: The aim of this study is to investigate the frequency of spinocerebellar ataxia (SCA) 2, 3 and 7 among Slovak patients with cerebellar ataxia of unknown origin.

Background: SCA types 2, 3 and 7 belong to a group of neurodegenerative disorders associated with a (CAG)_n repeat expansion in the coding sequence. They are one of the most prevalent autosomal dominant ataxias worldwide characterized by a broad range of symptoms, including cerebellar syndrome, pyramidal and extrapyramidal signs, or peripheral neuropathy [1].

Method: DNA samples from 41 patients with cerebellar ataxia of unknown origin from 2 tertiary movement disorders centres (Kosice and Zvolen, Slovakia) involved in the CEGEMOD study [2] were analysed to establish the number of CAG repeats in ATX2, ATX3 and ATX7 genes using Tethering PCR [3].

Results: We identified 1 patient with SCA2 (1/41 = 2.44%), carrying 38 CAG repeats in the ATX2 gene. The age of onset was in the fourth decade as a slowly progressive weakness of the lower limbs, gait instability and speech problems, with a negative family history. Neurological examination revealed dysarthric speech, ataxia with intention tremor on the upper limbs, ataxic gait with severe instability, asymmetric flaccid quadriparesis with hyporeflexia, hypesthesia of lower limbs and bladder dysfunction. No signs of parkinsonism or dystonia were present [4]. Brain MRI showed significant olivopontocerebellar atrophy. Additionally, EMG was performed to verify axonal sensory neuropathy. We did not identify any cases of SCA3 or SCA7 in our cohort.

Conclusion: Our data suggest that SCA 2, 3 and 7 are rare in Slovak patients of spinocerebellar ataxia compared to other European countries with the majority of index cases (40/41 = 97.5%) remaining undiagnosed. The frequency of SCA2 cases in our cohort was approx. 2.44% compared to 10-20% frequency of all SCA cases reported in cohorts across Europe as the second most frequent type of spinocerebellar ataxia [5]. Interestingly, the most frequent type in Western Europe – SCA3 [6], was not present in our cohort. To our knowledge, this is the first patient with SCA2 reported from Slovakia.

Acknowledgements

This project was supported by the Slovak Grant and Development Agency under contract no. APVV-22-0279 and by the Slovak Scientific Grant Agency under contract no. VEGA 1/0712/22.

References: [1] Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019 Feb;266(2):533-544. doi: 10.1007/s00415-018-9076-4.
[2] Skorvanek M, Rizig M, Athanasiou-Fragkouli A, Necpal J, Straka I, Tamas G, Kurca E, Mosejova A, Han V, Lorincova T, Ostrozovicova M, Liesenerova S, Levicka P, Fajcikova L, Minar M, Valkovic P, Mákos O, Kelemen A, Grofik M, Cibulka M, Jama F, Houlden H; members of the CEGEMOD study group. LRRK2 mutations in Parkinson’s disease patients from Central Europe: A case control study. Parkinsonism Relat Disord. 2021 Feb;83:110-112. doi: 10.1016/j.parkreldis.2020.12.021.
[3] Cagnoli C, Brussino A, Mancini C, et al. Spinocerebellar Ataxia Tethering PCR: A Rapid Genetic Test for the Diagnosis of Spinocerebellar Ataxia Types 1, 2, 3, 6, and 7 by PCR and Capillary Electrophoresis. J Mol Diagn. 2018;20(3):289-297. doi:10.1016/j.jmoldx.2017.12.006.
[4] Markovic V, Dragasevic-Miskovic NT, Stankovic I, Petrovic I, Svetel M, Kostić VS. Dystonia in Patients With Spinocerebellar Ataxia Type 2. Mov Disord Clin Pract. 2015 Dec 14;3(3):292-295. doi: 10.1002/mdc3.12274.
[5] Velázquez-Pérez LC, Rodríguez-Labrada R, Fernandez-Ruiz J. Spinocerebellar Ataxia Type 2: Clinicogenetic Aspects, Mechanistic Insights, and Management Approaches. Front Neurol. 2017 Sep 11;8:472. doi: 10.3389/fneur.2017.00472.
[6] Klockgether, T., Mariotti, C. & Paulson, H.L. Spinocerebellar ataxia. Nat Rev Dis Primers 5, 24 (2019). https://doi.org/10.1038/s41572-019-0074-3

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MDS Abstracts - https://www.mdsabstracts.org/abstract/frequency-of-sca-2-3-and-7-in-slovak-patients-with-spinocerebellar-ataxia-first-report-of-sca2-patient-from-slovakia/