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The Cerebellum

25-09-2024 | Research

Spinocerebellar Ataxia in Brazil: A Comprehensive Genotype – Phenotype Analysis

Authors: Maria Carolina Da Cunha Ganimi, Christian Marques Couto, Alessandra de La Rocque Ferreira, Carmen Lucia Antão Paiva

Published in: The Cerebellum

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Abstract

Spinocerebellar ataxias (SCAs) are a diverse group of hereditary neurodegenerative disorders characterized by progressive degeneration of the cerebellum and other parts of the nervous system. In this study, we examined the genotype‒phenotype correlations in SCAs within the Brazilian population by leveraging a comprehensive dataset of 763 individuals from SARAH Network of Rehabilitation Hospitals. Using a retrospective, cross-sectional, observational, multicentric approach, we analysed medical records and conducted standardized molecular testing to explore epidemiological characteristics, clinical manifestations, and genetic profiles of SCAs in Brazil. Our findings revealed the predominance of SCA3, followed by SCA7 and SCA2, which aligns with global trends and reflects the specific genetic landscape of Brazil. A significant inverse relationship between the age of symptom onset and CAG repeat length in the mutated allele was observed across SCAs 2, 3, and 7. This study also highlights a trend towards paternal inheritance in SCA2 and details the distribution of CAG repeat expansions, which correlates larger expansions with earlier onset and specific symptomatology. This extensive analysis underscores the critical importance of genetic testing in the diagnosis and management of SCAs and enlightens the intricate genotype‒phenotype interplay within a genetically diverse population. Despite certain limitations, such as potential selection bias and the retrospective nature of the study, our research provides invaluable insights into the prevalence, genetic underpinnings, and clinical variability of SCAs in Brazil. We suggest a broader demographic scope and investigations into nonmotor symptoms in future studies to obtain a more comprehensive understanding of SCAs.
Literature
1.
Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266(2):533–44.CrossRefPubMed
2.
Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174–83.CrossRefPubMed
3.
Scott SSO, Pedroso JL, Barsottini OGP, Franca-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: insights from the first description to nowadays. J Neurol Sci. 2020;417:117082.CrossRefPubMed
4.
5.
Rossi M, Perez-Lloret S, Doldan L, Cerquetti D, Balej J, Millar Vernetti P, et al. Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur J Neurol. 2014;21(4):607–15.CrossRefPubMed
6.
7.
Ashizawa T, Figueroa KP, Perlman SL, Gomez CM, Wilmot GR, Schmahmann JD, et al. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;8:177.CrossRefPubMedPubMedCentral
8.
Buijsen RAM, Toonen LJA, Gardiner SL, van Roon-Mom WMC, Genetics. Mechanisms, and therapeutic progress in polyglutamine Spinocerebellar Ataxias. Neurotherapeutics. 2019;16(2):263–86.CrossRefPubMedPubMedCentral
9.
de Castilhos RM, Furtado GV, Gheno TC, Schaeffer P, Russo A, Barsottini O, et al. Spinocerebellar ataxias in Brazil–frequencies and modulating effects of related genes. Cerebellum. 2014;13(1):17–28.CrossRefPubMed
10.
Figueroa KP, Coon H, Santos N, Velazquez L, Mederos LA, Pulst SM. Genetic analysis of age at onset variation in spinocerebellar ataxia type 2. Neurol Genet. 2017;3(3):e155.CrossRefPubMedPubMedCentral
11.
Netravathi M, Pal PK, Purushottam M, Thennarasu K, Mukherjee M, Jain S. Spinocerebellar ataxias types 1, 2 and 3: age adjusted clinical severity of disease at presentation correlates with size of CAG repeat lengths. J Neurol Sci. 2009;277(1–2):83–6.CrossRefPubMed
12.
Sinke RJ, Ippel EF, Diepstraten CM, Beemer FA, Wokke JH, van Hilten BJ, et al. Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families. Arch Neurol. 2001;58(11):1839–44.CrossRefPubMed
13.
Tezenas du Montcel S, Durr A, Bauer P, Figueroa KP, Ichikawa Y, Brussino A, et al. Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes. Brain. 2014;137(Pt 9):2444–55.CrossRefPubMedPubMedCentral
14.
van de Warrenburg BP, Hendriks H, Durr A, van Zuijlen MC, Stevanin G, Camuzat A, et al. Age at onset variance analysis in spinocerebellar ataxias: a study in a dutch-french cohort. Ann Neurol. 2005;57(4):505–12.CrossRefPubMed
15.
Luo L, Wang J, Lo RY, Figueroa KP, Pulst SM, Kuo PH, et al. The initial Symptom and Motor Progression in Spinocerebellar Ataxias. Cerebellum. 2017;16(3):615–22.CrossRefPubMedPubMedCentral
16.
Stevanin G, Durr A, Brice A. Chapter 4 clinical and genetic aspects of spinocerebellar ataxias with emphasis on polyglutamine expansions. In: Alexis B, S-MP, editors. Spinocerebellar degenerations: the ataxias and Spastic paraplegias. Blue Books of Neurology. Volume 31. Butterworth-Heinemann; 2007. pp. 113–44.
17.
Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology. 2011;77(11):1035–41.CrossRefPubMedPubMedCentral
18.
Diallo A, Jacobi H, Cook A, Labrum R, Durr A, Brice A, et al. Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study. Lancet Neurol. 2018;17(4):327–34.CrossRefPubMed
19.
Jardim LB, Hauser L, Kieling C, Saute JA, Xavier R, Rieder CR, et al. Progression rate of neurological deficits in a 10-year cohort of SCA3 patients. Cerebellum. 2010;9(3):419–28.CrossRefPubMed
20.
Nascimento FA, Rodrigues VOR, Pelloso FC, Camargo CHF, Moro A, Raskin S, et al. Spinocerebellar ataxias in Southern Brazil: genotypic and phenotypic evaluation of 213 families. Clin Neurol Neurosurg. 2019;184:105427.CrossRefPubMed
21.
Cintra VP, Lourenco CM, Marques SE, de Oliveira LM, Tumas V, Marques W. Jr. Mutational screening of 320 Brazilian patients with autosomal dominant spinocerebellar ataxia. J Neurol Sci. 2014;347(1–2):375–9.CrossRefPubMed
22.
Teive HA, Munhoz RP, Arruda WO, Lopes-Cendes I, Raskin S, Werneck LC, et al. Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families. Clin (Sao Paulo). 2012;67(5):443–9.CrossRef
23.
Souza GN, Kersting N, Krum-Santos AC, Santos AS, Furtado GV, Pacheco D, et al. Spinocerebellar ataxia type 3/Machado-Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions. Clin Genet. 2016;90(2):134–40.CrossRefPubMed
24.
Rangel DM, Nobrega PR, Saraiva-Pereira ML, Jardim LB, Braga-Neto P. A case series of hereditary cerebellar ataxias in a highly consanguineous population from Northeast Brazil. Parkinsonism Relat Disord. 2019;61:193–7.CrossRefPubMed
25.
26.
27.
Shakkottai VG, Fogel BL. Clinical neurogenetics: autosomal dominant spinocerebellar ataxia. Neurol Clin. 2013;31(4):987–1007.CrossRefPubMed
28.
Teive HAG, Meira AT, Camargo CHF, Munhoz RP. The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas: a systematic review. Mov Disord Clin Pract. 2019;6(7):531–40.CrossRefPubMedPubMedCentral
29.
Paradisi I, Ikonomu V, Arias S. Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent. J Hum Genet. 2016;61(3):215–22.CrossRefPubMed
30.
Bryer A, Krause A, Bill P, Davids V, Bryant D, Butler J, et al. The hereditary adult-onset ataxias in South Africa. J Neurol Sci. 2003;216(1):47–54.CrossRefPubMed
31.
Ikeda Y, Ranum LP, Day JW. Clinical and genetic features of spinocerebellar ataxia type 8. Handb Clin Neurol. 2012;103:493–505.CrossRefPubMed
32.
Boonkongchuen P, Pongpakdee S, Jindahra P, Papsing C, Peerapatmongkol P, Wetchaphanphesat S, et al. Clinical analysis of adult-onset spinocerebellar ataxias in Thailand. BMC Neurol. 2014;14:75.CrossRefPubMedPubMedCentral
33.
Globas C, du Montcel ST, Baliko L, Boesch S, Depondt C, DiDonato S, et al. Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov Disord. 2008;23(15):2232–8.CrossRefPubMed
34.
Mutesa L, Pierquin G, Segers K, Vanbellinghen JF, Gahimbare L, Bours V. Spinocerebellar ataxia type 2 (SCA2): clinical features and genetic analysis. J Trop Pediatr. 2008;54(5):350–2.CrossRefPubMed
35.
Durr A, Stevanin G, Cancel G, Duyckaerts C, Abbas N, Didierjean O, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol. 1996;39(4):490–9.CrossRefPubMed
36.
Maciel P, Gaspar C, DeStefano AL, Silveira I, Coutinho P, Radvany J, et al. Correlation between CAG repeat length and clinical features in Machado-Joseph disease. Am J Hum Genet. 1995;57(1):54–61.PubMedPubMedCentral
37.
Tezenas du Montcel S, Durr A, Rakowicz M, Nanetti L, Charles P, Sulek A, et al. Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6. J Med Genet. 2014;51(7):479–86.CrossRefPubMed
38.
de Mattos EP, Leotti VB, Soong BW, Raposo M, Lima M, Vasconcelos J, et al. Age at onset prediction in spinocerebellar ataxia type 3 changes according to population of origin. Eur J Neurol. 2019;26(1):113–20.CrossRefPubMed
39.
Martin J, Van Regemorter N, Del-Favero J, Lofgren A, Van Broeckhoven C. Spinocerebellar ataxia type 7 (SCA7) - correlations between phenotype and genotype in one large Belgian family. J Neurol Sci. 1999;168(1):37–46.CrossRefPubMed
Metadata
Title
Spinocerebellar Ataxia in Brazil: A Comprehensive Genotype – Phenotype Analysis
Authors
Maria Carolina Da Cunha Ganimi
Christian Marques Couto
Alessandra de La Rocque Ferreira
Carmen Lucia Antão Paiva
Publication date
25-09-2024
Publisher
Springer US
Published in
The Cerebellum
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-024-01745-3

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