Epidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic review and Meta-analysis

Epidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Epidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic review and Meta-analysis Milagros Galecio-Castillo, Jesus Gutierrez-Arratia, Alonso Abad-Murillo, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5946715/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant neurodegenerative disorders characterized by progressive cerebellar ataxia, affecting motor coordination. SCAs are reported globally with large geographical and ethnic differences. This systematic review and meta-analysis aimed to update the frequency, and geographic distribution of SCAs in Latin America, including recently identified SCAs like SCA27b. We conducted a systematic search in PubMed, Scopus, LILACS, SciELO and Web of Science databases, including studies published from inception to January 2025. We included 25 studies for the systematic review and 17 studies for the meta-analysis that met the inclusion criteria, representing a total of 5,546 participants across eleven countries. Our meta-analysis revealed that about 61% (95% CI 31–84%) of hereditary ataxias in Latin America were confirmed to have a genetic diagnosis of SCA. The included participants with a known SCA have the following proportions: MJD/SCA3 (34%), SCA2 (30%), SCA10 (9%), SCA7 (9%) and SCA1 (4%). Geographic distributions were notable, MJD/SCA3 in Brazil, SCA2 in Cuba, Argentina and Mexico, SCA10 predominating in Peru, and SCA7 in Venezuela. Recently identified subtypes, like SCA27B and one case of SCA4, were identified in Brazil. In 22 countries there are no published studies on the epidemiology of SCAs. The distribution of SCAs in Latin America reflects the influence of historical migrations, founder effects, and ancestries, emphasizing regional heterogeneity. Our findings underscore the critical need for further epidemiological studies, particularly in understudied countries in the region. Molecular Epidemiology Medical Genetics Neurology Epidemiology Statistical Epidemiology SCA Spinocerebellar ataxia epidemiology Latin America systematic review meta-analysis Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant hereditary ataxias characterized by impairments in the coordination of voluntary movements caused by progressive degeneration of the cerebellum and its associated pathways [ 1 ]. To date, about 50 genetically distinct subtypes have been identified, with largely variable clinical features ranging from pure cerebellar syndromes to more complex forms [ 2 ]. Epidemiological studies on SCAs reveal significant geographic and ethnic differences, with variations in prevalence attributable to founder effects, diverse migrations patterns and the occurrence of some clusters of SCAs [ 3 ]. Globally, the Spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD/SCA3) is the most commonly reported SCA, followed by SCA2 and SCA6 [ 1 , 4 , 5 ], with significant geographical differences. By contrast, in Asia and Europe, other SCAs such as SCA1, SCA12 and SCA31 have been reported with largest frequencies [ 6 , 7 ]. A comprehensive review of inherited ataxias in the Pan-American region, published in 2019, highlighted a high prevalence of MJD/SCA3 in Brazil, SCA2 in Cuba, and SCA10 in populations with Amerindian ancestry, including those in Peru, Mexico, and Brazil [ 8 ]. However, this review did not include some recently identified SCAs, such as SCA27B [ 9 , 10 ] and SCA4 [ 11 – 13 ], underscoring the need for updated and expanded research to capture the evolving genetic landscape of inherited ataxias in the region. Despite significant advances in the study of SCAs, there remains a notable lack of epidemiological research in most Latin American countries. This gap limits our understanding of the current prevalence of SCAs and their regional variations across diverse geographic areas and known clusters. This study aims to systematically review the literature on the epidemiology of SCAs throughout Latin America. By analyzing existing data, we seek to estimate the frequency and geographic distribution of the most common SCAs by country. In addition, we aim to identify regions with limited or no studies, highlighting areas where further epidemiological research is needed. MATERIALS AND METHODS This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines (PRISMA) [ 14 ]. The study has been registered on PROSPERO with ID number CRD42024473971. Eligibility criteria and study variables We included published studies that (I) were written in any language; (II) directly investigated dominant spinocerebellar ataxias or SCAs in population residing in Latin America, including the Caribbean countries; (III) had one of the following designs: case reports (including isolated cases), case series (≥ 5 participants for the meta-analysis), observational studies, or experimental studies; and (IV) were published from inception to January 2025. We excluded studies that: (I) lack a definitive diagnosis of SCA through genetic testing; (II) other designs such as review articles, conference abstracts, or research proposals; and (III) studies mainly focused on other regions outside of Latin America. The study variables included: (I) demographic characteristics (age, sex, and geographic location); (II) genetic subtype of SCA (e.g. SCA2, MJD/SCA3, SCA6, DRPLA, SCA10); and (III) clinical outcomes, including diagnostic methods and prevalence rates. Unknown genetic diagnosis was considered only if explicitly specified by the authors. Search strategy, studies’ review and selection We conducted a systematic electronic literature search by entries to PubMed, Scopus, LILACS, SciELO, and Web of Science, through January 2025. No language restrictions were used, and translation was arranged when necessary. To achieve a comprehensive review, we screened the reference list of relevant records as well. The complete search strategies are detailed in the Supplementary Table 1 . Three independent reviewers (J.G-A., A.A-M. and M.G-C.) screened all identified records and conducted full-text assessment of the pre-selected studies using the web-based application Rayyan (rayyan.qcri.org) [ 15 ], which systematically detects, and flags suspected duplicate records. The reviewers carried out data extraction using a data collection tool previously designed and cross-checked the extracted data. Disagreements over study selection were solved by a senior reviewer (M.C-O.). Study quality and risk of bias assessment The studies included in this systematic review were assessed for risk of bias using the tool [ 16 ]. Two independent reviewers (J.G-A. and E.S-C.) conducted the assessments, evaluating ten domains such as study design, population sampling and data collection method. Each domain was rated as either “low” or “high” risk. A summary score was then used to classify studies into three categories: Low risk of bias, moderate risk of bias, and high risk of bias. Disagreements between reviewers were resolved through consultation with a third reviewer (M.C-O.). Data analysis For studies included in the meta-analysis, we pooled the prevalence rates and calculated a weighted overall proportion with 95% CIs. Due to the small number of events and differences in sample size between studies, we used generalized linear mixed models transformations [ 17 , 18 ]. We used fixed- and random-effects models, and calculated prediction intervals for each meta-analysis. Subgroup meta-analyses were conducted with stratification by SCA type when more than two studies reported the data of interest. Heterogeneity Assessment and Publication bias Heterogeneity across studies was assessed using the I² statistic, which measures the percentage of total variability due to between-study heterogeneity. The Tau² was also calculated to estimate the variance between studies, with a significance level at P < 1.0. Due to the limitations of funnel plots for assessing proportion meta-analysis, we evaluated publication bias through Doi Plots and the LFK index [ 19 , 20 ]. All statistical analyses were conducted using R Statistical Software (version 4.3.3) and RStudio (R Foundation for Statistical Computing, Vienna, Austria). Figures and illustrations were generated using R Statistical Software and QGIS. Certainty of evidence synthesis Following Cochrane recommendations, 2 reviewers (M.G-C. and J.G-A) independently evaluated the quality of the body of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. The GRADEpro online tool ( http://gradepro.org ) was employed to facilitate a structured assessment. Evidence was graded as high, moderate, low or very low. RESULTS Study selection We identified 803 records through a systematic research approach. After removing duplicates, we screened 663 records and retrieved 39 articles for full-text assessment. In addition, we identified 6 articles through grey literature search (manual search). Of those, a total of 25 studies were included in the systematic review, and 17 in the meta-analysis (Supplementary Figure 1) . The studies excluded from the meta-analysis were case reports, focused on participants with a specific SCA, overlapped with other studies included in the meta-analysis (in which case we chose the biggest study for the meta-analysis), or reported data of families. Risk of bias The included studies were assessed for risk of bias using the adapted tool for prevalence studies by Hol et. al [16]. Of the 17 studies analyzed, ten were classified as having high risk of bias, and the remaining seven as moderate risk. Issues related to external validity were common, primarily due to the regional nature of the populations studied, which lacked clear evidence of national representativeness, limiting the generalizability of findings. On the other hand, internal validity issues were associated with insufficient descriptions of the prevalence period, lack of validation of the measurement instruments used, and the absence of clear reporting of the populations included in prevalence calculations. Supplementary Table 2 provides a detailed assessment of the risk of bias for each included study. Studies’ characteristics Descriptive characteristics of the 25 included studies are displayed in Table 1 . They provided data from 5,526 ataxic cases from eleven countries: Brazil (9), Mexico (4), Peru (3), Chile (2), Argentina (2), Cuba (2), Uruguay (1), Venezuela (1), Colombia (1), and Ecuador (1). Of those, Avila Jaque et al. included participants from both Chile and Mexico, and Sena et al. from Peru, Chile, and Uruguay. The median age of symptoms onset ranged from 23 to 59.9 years old, and 33.3-60% were women. Meta-analysis Out of 17 studies, the SCA types reported and included in the meta-analysis were MJD/SCA3 (13 studies), SCA2 (13 studies), SCA7 (12 studies), SCA1 (9 studies), SCA10 (8 studies), SCA6 (7 studies), SCA8 (2 studies), DRPLA (3 studies), SCA28 (2 studies), as well as SCA4, SCA5, SCA 17, SCA21, SCA27, SCA27b, SCA31, SCA36, SCA42, SCA48, and (1 study each). The 17 studies reported data of 3,880 ataxic cases. The diagnosis index was 61% (95% CI 31-84%), and 39% (95% CI 16-69%) remained as an unknown genetic diagnosis at the time the studies took place (Figure 1) . When stratifying by type of SCA among all confirmed cases, we found that the most common SCAs in Latin America were MJD/SCA3 (34%, 95% CI 14-62%), and SCA2 (30%, 95% CI 11-59%), followed by SCA10 (9%, 95% CI 3-24%) and SCA7 (9%, 95% CI 4-20%). Other reported SCAs included SCA1 (4%, 95% CI 2-10%), DRPLA (4%, 95% CI 2-6%), and SCA 6 (3%, 2-5%). (Figure 2) . Regarding SCA distribution by country of origin, we found that SCA2 was most frequently reported in Cuba, MJD/SCA3 in Brazil, Argentina and Mexico, and SCA10 in Peru. (Figure 3) . Certainty of evidence Certainty of the evidence was low or very low for all the meta-analyses. These results are mainly driven by a moderate-high risk of bias found in all the studies and further downgraded by the design of our work and all the included studies (Supplementary Table 3). In addition, large confidence interval found in the random effect models influenced the certainty of evidence results; although we could have excluded studies where a very low rate was reported, most likely due to lack of access to genetic testing, the authors decided to include them in the meta-analyses to ensure that our study reflects the current state of the available literature. DISCUSSION We conducted a systematic review and meta-analysis aiming to estimate the frequency and geographic distribution of dominant spinocerebellar ataxias or SCAs in the Latin American region. Our results suggested that SCA2, MJD/SCA3, SCA10, SCA7, and SCA1 are the most prevalent SCAs, with significant geographical variations across and within countries. Importantly, we could not include nor one published study in 22 countries of the Latin American region, presumably related to challenges on diagnostic procedures, lack of access to specialized care, scarce local researchers in the field, scientific papers published in local non-indexed journals, overwhelming work for clinicians preventing them to actively participant in research, funding limitations and language barriers, among others [21–23]. MJD/SCA3. Our results showed that MJD/SCA3 is the most frequent SCA reported in Latin America (34% of pooled cases), with significant variations by regions. Brazil, mainly the southern region, reported a large prevalence of MJD/SCA3 in Latin America, representing 45-73% of all identified SCAs in this region [24,25]. MJD/SCA3 was originally reported in three families from the Portuguese Azores islands, and Asian populations [26], this disease which later spread through migrations to Europe, United States and southern Brazil over the last centuries [27]. Haplotype studies performed in the MJD/SCA3 Brazilian cases, identified ancestral mutation within both Machado and Joseph lineage tracing its origin to Portugal and Asia [28]. MJD/SCA3 was also reported in Cuba, Chile, Venezuela, Mexico, Argentina and Peru. Countries with almost no history of Portuguese colonization, like Peru reported very few MJD/SCA3 cases [29]. SCA2. A high prevalence of SCA2 has been reported in Latin America becoming the second most frequent SCA in the region. SCA2 is the most common subtype in Cuba, Mexico, and Argentina. Worldwide, SCA2 is the second most common subtype of spinocerebellar ataxia and is widely distributed across Europe, India, and South Korea [6,7]. The Cuban population, with a known African and European ancestry, exhibits the highest reported prevalence of SCA2 worldwide, accounting for about 86% of all identified SCAs [8]. [26]. The Holguin region in Cuba hosts a well-documented cluster for SCA2, where prevalence reaches 154.3 per 100,000 inhabitants. This clustering has been attributed to a strong founder effect, likely introduced during Spanish colonization, combined with high rates of endogamy. Haplotype studies confirm genetic similarities between Cuban and Spanish populations, supporting this historical connection [26]. SCA2 is also highly prevalent in Mexico and Argentina, likely influenced by Spanish ancestry and potential founder effects coming from Europe [31,32]. In Peru, SCA2 represents the second most commonly diagnosed SCA, possibly reflecting the influence of the Spanish European colonizers, as well as some other migration patterns from non-Hispanic Europeans [23]. SCA10 . Our review identified approximately 7% of all the Latin American SCA cases corresponds to SCA10, being reported as the most prevalent SCA in Peru, and about the top two in Mexico and Brazil, consistent with the known association of SCA10 with Native American ancestry [33]. Haplotype studies have revealed a shared ancestor from both East Asia and the Americas, suggesting that the pathogenic expanded ATTCT tract may have occurred before the divergence of proto-Amerindian populations [26]). In the southern region of Brazil, including Paraná and Santa Carina –(the gathering of SCA10 in Brazil)- the SCA10 cases exhibit a pure cerebellar ataxia [34], whereas Mexican phenotype includes seizures [35]. In Peru, the high frequency of SCA10 could be associated with the high Native American ancestry (above 50% on average) [36]. We identified a Bolivian family with SCA10, with at least 2 affected family members also harbor an ATXN2 expansion [37]. No other representative cohorts have been described in Latin American, other SCA10 families have been reported in Bolivia [37], Argentina [38], Colombia [39] and Venezuela [40]. SCA7. Overall SCA7 represents 7% of all SCA cases in Latin America. We found that SCA7 is the most frequent form of SCA in Venezuela and has also been reported with high frequency in Brazil and southeastern Mexico, with lower frequencies in Peru, Argentina and Cuba. Haplotype based studies performed in the two SCA7 clusters in Venezuela, were caused by founder effect (Paradisi et al., 2016). Several studies suggested that migrations patterns and founder effects coming from Europe and South Africa could explain the high relative frequencies of SCA7 [6,40,41]. More than 60% of the SCA7 families in Brazil derived from a region on Northeastern Brazil, where a high inbreeding level was reported [42]. In Veracruz (southeastern Mexico), SCA7 has a documented cluster with an estimated prevalence of 423 per 100,000 inhabitants, likely explained by founder effects linked to Basque and French ancestry [26,43,44]. SCA1 accounts for 4% of SCAs in Latin America. Most of cases reside in Brazil, Venezuela, Argentina, with rarely and isolated families in Cuba and Peru. Worldwide SCA1 is mostly prevalent in Poland, Serbia, Russia and Northen Italy [45,45–48]. Ancestor markers analysis in SCA1 suggest suggests a founder effect in Central Poland [49]. The occurrence of SCA1 in Latin American countries may be mostly related to migration phenomenon, there are no specific clusters or regions in significantly higher frequencies of SCA1. SCA6 has a low frequency in Latin America, accounting for 2% of all diagnosed SCAs, being mostly reported in Brazil, Argentina and Peru. Many SCA6 cases comes from extended family clinical characterizations, with frequency history of Asian ancestors. The typical very late onset of SCA6, together with absence of family history, may increase the risk of misdiagnosis of SCA6 [50]. Dentatorubropallidoluysian ataxia or DRPLA is highly prevalent among Japanese population and in is rarely found in non-Japanese pedigrees with cases described in North America and Europe [51,52]. We identified only 10 cases affected wit, about 8 come from Brazil, with the majority of them declaring a Japanese ancestry. Interestingly, in Venezuela, 2 cases were reported with large family history of apparent just Venezuelan ancestry [40]. By contrast, other countries like Peru, also harboring a large Japanese community, do not identify DRPLA cases. We cannot exclude that fact of underdiagnosis component in DRPLA, as in other countries in the region [53]. Recently identified SCAs. SCA27B is recently(2022) identified dominant ataxia caused by an intronic GAA repeat expansion within the FGF14 gene [9,10]. Recent studies in European and Asian populations have suggested that SCA27b might be one of the most common autosomal dominant ataxias. Worldwide, SCA27B has relative frequencies almost similar to common SCAs such as SCA3/MJD, SCA1, SCA6, and SCA2 in Franco-Canadian [10], Australian [9], German [54], French [55], Spanish [56] cohorts. In Brazil, SCA27B was recently identified as part of the expanding spectrum of genetic causes for late-onset ataxia [57]. Among the nine Brazilian SCA27b, the majority of them were of European descent, consistent with the hypothesis of a European origin for this disease [10,37,44]. A non-consanguineous ataxia family was reported in Chile, in which FGF14 genetic analysis revealed an expanded allele with non-GAA motifs, that currently are considered non-pathogenic [9,10,58,59]. Despite the locus linked to SCA4 was reported back in 1996 [60], the GGC-repeat expansion in the ZFHX3 gene was recently (2023) identified by two groups in Sweden and Germany [61–64]. To date there is only one SCA4 case report identified in Brazil [13]. We found one Brazilian publication reporting 2 cases with SCA45, however the origin of each patient is not specified in the manuscript [65]. Strength and limitations The results of our review highlight both strengths and critical gaps related to the applied methodology and the limited availability of published studies on SCAs in Latin America. Our systematic approach provides updated epidemiological insights, including data on recently identified SCAs such as SCA27b and SCA4. However, due to insufficient epidemiological data, we were unable to estimate prevalence rates for each country. Additionally, we acknowledge several challenges: variations in sample sizes, inconsistent access to genetic testing (making it difficult to rule out other autosomal dominant SCAs), and a general lack of published or updated data across most countries. Furthermore, potential unidentified overlaps among studies could influence results. To mitigate this, we focused on evaluating percentages rather than absolute numbers to provide a more standardized comparison. The absence of data from several Latin American countries and inconsistent access to genetic testing limits the broader understanding of SCAs in the region. Furthermore, methodological limitations in many studies, emphasize the need for standardize, multicentric research to establish national and continental prevalence rates. Due to inclusion criteria used for this systematic review we excluded cases residing outside Latin America as well as cases harboring more than one SCA mutation; reports of one American case of Colombian origin harboring ATXN10 and HTT expansion [66], and two German siblings of Colombian origin with SCA21 [67], 1 American family of Guatemalan origin with SCA10 [68]. Conclusion or summary In conclusion, our study provides a comprehensive analysis of the distribution and frequency of SCAs in Latin America. We identified MJD/SCA3, SCA2, SCA10, and SCA7 as the most prevalent SCAs in the region, with significant geographical variations both within and between countries. Our findings underscore the impact of historical, migratory, and genetic factors on the distribution of these diseases, as evidenced by founder effects in known clusters in the region. Moreover, our study highlights the strong association between specific ancestries and some SCAs, as occurred in SCA10 with consistent frequencies related to the Amerindian ancestry component. To date, recently identified SCAs, such as SCA27B and SCA4 were only reported in Brazil. Declarations Authors' contributions: All authors contributed to the conception of the study. M.G-C., J.G-A and A.A-M performed the literature search and data analysis. The first draft of the manuscript was written by M.G-C and J-G-A. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest: The authors declare no conflicts of interest regarding the present study. Acknowledgements This work was performed with academic support from Universidad Cientifica del Sur and logistic support of Instituto Nacional de Ciencias Neurologicas. The authors would like to thank Mahmoud Dibas (Neurology, University of Iowa Health Care, USA) for his support with conceptualization of the study. References Scott SS de O, Pedroso JL, Barsottini OGP, França-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: Insights from the first description to nowadays. J Neurol Sci [Internet]. 2020 [cited 2025 Jan 28];417. Available from: https://www.jns-journal.com/article/S0022-510X(20)30419-6/abstract Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266:533–44. Lima M, Raposo M, Ferreira A, Melo ARV, Pavão S, Medeiros F, et al. The Homogeneous Azorean Machado-Joseph Disease Cohort: Characterization and Contributions to Advances in Research. Biomedicines. 2023;11:247. 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Proc Natl Acad Sci. 2018;115:E6526–35. Baizabal-Carvallo JF, Xia G, Botros P, Laguna J, Ashizawa T, Jankovic J. Bolivian Kindred with Combined Spinocerebellar Ataxia Type 2 and 10. Acta Neurol Scand. 2015;132:139–42. Gatto EM, Gao R, White MC, Uribe Roca MC, Etcheverry JL, Persi G, et al. Ethnic origin and extrapyramidal signs in an argentinean spinocerebellar ataxia type 10 family. Neurology. 2007;69:216–8. Leiva LM, Zuluaga ME, Espinosa K, Delgado-Argote H, Ramirez-Cheyne J. Ataxia espinocerebelosa tipo 10 de inicio tardío. Rev Colomb Med Física Rehabil. 2022;32:208–14. Paradisi I, Ikonomu V, Arias S. Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent. J Hum Genet. 2016;61:215–22. Smith DC, Bryer A, Watson LM, Greenberg LJ. Inherited polyglutamine spinocerebellar ataxias in South Africa. South Afr Med J Suid-Afr Tydskr Vir Geneeskd. 2012;102:683–6. Santos S, Kok F, Weller M, Paiva FRL de, Otto PA. Inbreeding levels in Northeast Brazil: strategies for the prospecting of new genetic disorders. Genet Mol Biol. 2010;33:220–3. Magaña J j., Tapia-Guerrero Y s., Velázquez-Pérez L, Cerecedo-Zapata C m., Maldonado-Rodríguez M, Jano-Ito J s., et al. Analysis of CAG repeats in five SCA loci in Mexican population: epidemiological evidence of a SCA7 founder effect. Clin Genet. 2014;85:159–65. Magaña JJ, Gómez R, Maldonado-Rodríguez M, Velázquez-Pérez L, Tapia-Guerrero YS, Cortés H, et al. Origin of the Spinocerebellar Ataxia Type 7 Gene Mutation in Mexican Population. The Cerebellum. 2013;12:902–5. Dragašević NT, Čuljković B, Klein C, Ristić A, Keckarević M, Topisirović I, et al. Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients. Mov Disord. 2006;21:187–91. Illarioshkin SN, Slominsky PA, Ovchinnikov IV, Markova ED, Miklina NI, Klyushnikov SA, et al. Spinocerebellar ataxia type 1 in Russia. J Neurol. 1996;243:506–10. Krysa W, Sulek A, Rakowicz M, Szirkowiec W, Zaremba J. High relative frequency of SCA1 in Poland reflecting a potential founder effect. Neurol Sci. 2016;37:1319–25. Sułek-Piątkowska A, Zdzienicka E, Rakowicz M, Krysa W, Rajkiewicz M, Szirkowiec W, et al. The occurrence of spinocerebellar ataxias caused by dynamic mutations in Polish patients. Neurol Neurochir Pol. 2010;44:238–45. Sułek-Piątkowska A, Zdzienicka E, Rakowicz M, Krysa W, Rajkiewicz M, Szirkowiec W, et al. The occurrence of spinocerebellar ataxias caused by dynamic mutations in Polish patients. Neurol Neurochir Pol. 2010;44:238–45. Schöls L, Krüger R, Amoiridis G, Przuntek H, Epplen JT, Riess O. Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds. J Neurol Neurosurg Psychiatry. 1998;64:67–73. Wardle M, Morris HR, Robertson NP. Clinical and genetic characteristics of non-Asian dentatorubral-pallidoluysian atrophy: A systematic review. Mov Disord. 2009;24:1636–40. Becher MW, Rubinsztein DC, Leggo J, Wagster MV, Stine OC, Ranen NG, et al. Dentatorubral and pallidoluysian atrophy (DRPLA) Clinical and neuropathological findings in genetically confirmed north american and european pedigrees. Mov Disord. 1997;12:519–30. Pinto WBV de R, Salomão RPA, Bergamasco NC, Ribas G da C, Graça FF da, Lopes-Cendes I, et al. DRPLA: An unusual disease or an underestimated cause of ataxia in Brazil? Parkinsonism Relat Disord. 2021;92:67–71. Hengel H, Pellerin D, Wilke C, Fleszar Z, Brais B, Haack T, et al. As Frequent as Polyglutamine Spinocerebellar Ataxias: SCA27B in a Large German Autosomal Dominant Ataxia Cohort. Mov Disord. 2023;38:1557–8. Méreaux J-L, Davoine C-S, Pellerin D, Coarelli G, Coutelier M, Ewenczyk C, et al. Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions. eBioMedicine [Internet]. 2024 [cited 2025 Jan 29];99. Available from: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00497-8/fulltext Iruzubieta P, Pellerin D, Bergareche A, Albajar I, Mondragón E, Vinagre A, et al. Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia. Eur J Neurol. 2023;30:3828–33. Novis LE, Frezatti RS, Pellerin D, Tomaselli PJ, Alavi S, Della Coleta MV, et al. Frequency of GAA-FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia. Neurol Genet. 2023;9:e200094. Saffie Awad P, Lohmann K, Hirmas Y, Hinrichs F, Thomsen M, Kauffman M, et al. Shaking Up Ataxia: and Repeat Expansions in Affected and Unaffected Members of a Chilean Family. Mov Disord. 2023;38:1107–9. Pellerin D, Iruzubieta P, Tekgül Ş, Danzi MC, Ashton C, Dicaire M-J, et al. Non-GAA Repeat Expansions in Are Likely Not Pathogenic—Reply to: “Shaking Up Ataxia: and Repeat Expansions in Affected and Unaffected Members of a Chilean Family.” Mov Disord. 2023;38:1575–7. Flanigan K, Gardner K, Alderson K, Galster B, Otterud B, Leppert MF, et al. Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet. 1996;59:392–9. Wallenius J, Kafantari E, Jhaveri E, Gorcenco S, Ameur A, Karremo C, et al. Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease. Am J Hum Genet. 2024;111:82–95. Chen Z, Gustavsson EK, Macpherson H, Anderson C, Clarkson C, Rocca C, et al. Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in Associated with Spinocerebellar Ataxia Type 4. Mov Disord. 2024;39:486–97. Paucar M, Nilsson D, Engvall M, Laffita-Mesa J, Söderhäll C, Skorpil M, et al. Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs. J Intern Med. 2024;296:234–48. Figueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Kakar N, et al. A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nat Genet. 2024;56:1080–9. Tonholo Silva TY, Rosa ABR, Quaio CR, Verbeek D, Pedroso JL, Barsottini O. Does SCA45 Cause Very Late-Onset Pure Cerebellar Ataxia? Neurol Genet. 2021;7:e581. Roxburgh RH, Smith CO, Lim JG, Bachman DF, Byrd E, Bird TD. The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease. J Neurol Sci. 2013;324:176–8. Traschütz A, Gaalen J van, Oosterloo M, Vreeburg M, Kamsteeg E-J, Deininger N, et al. The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature. Parkinsonism Relat Disord. 2019;62:215–20. Trikamji B, Singh P, Mishra S. Spinocerebellar ataxia-10 with paranoid schizophrenia. Ann Indian Acad Neurol. 2015;18:93. Velázquez-Pérez L, Medrano-Montero J, Rodríguez-Labrada R, Canales-Ochoa N, Campins Alí J, Carrillo Rodes FJ, et al. Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients. The Cerebellum. 2020;19:252–64. 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. The Cerebellum. 2014;13:17–28. Tables Table 1. Summary of the studies included in the systematic review and meta-analysis Country Participants (N) SCA types SCA (n) SCA (%) Median age at onset Women (%) Risk of bias Studies included in the Systematic Review and Meta-analysis Alonso 2007 Mexico 108 SCA2 49 45.4 Moderate SCA10 15 13.9 MJD/SCA3 13 12 SCA7 15 7.4 Alvarenga 2022 Brazil 153 MJD/SCA3 107 69.9 40.7 54.6 High SCA7 9 16.3 38.5 SCA2 5 5.8 23 Cornejo-Olivas 2020 Peru 56 SCA10 27 48.2 42 Moderate SCA2 8 14.3 24 SCA7 5 8.9 20 Cornejo-Olivas 2022 Peru 341 MJD/SCA3 18 5.3 46.3 33.3 Moderate de Castilhos 2014 Brazil 359 MJD/SCA3 214 59.6 34 Moderate SCA2 28 7.8 29.7 SCA7 20 5.5 25.5 Magaña 2014 Mexico 64 SCA7 55 85.9 32.7 High SCA2 9 14.1 Massuyama 2024 Brazil 328 MJD/SCA3 170 51.8 High SCA2 60 18.3 SCA7 39 11.9 Miranda 2015 Chile 50 SCA3 10 20 45 50 High Moraes 2023 Brazil 73 MJD/SCA3 55 75.3 37.6 54.7 High SCA7 11 15.1 25.7 SCA1 5 6.8 33.2 Nascimiento 2019 Brazil 460 MJD/SCA3 210 45.7 35.3 47.1 High SCA10 84 18.2 35.2 53.6 Novis 2023 Brazil 93 SCA27B 9 9.7 59.9 44.4 High Paradisi 2016 Venezuela 85 SCA7 25 29.4 30.6 Moderate SCA2 18 21.2 27.4 MJD/SCA3 16 18.8 39 SCA1 15 17.6 41.6 Perez Maturo 2020 Argentina 55 SCA2 20 36.4 30.7 54.5 High MJD/SCA3 10 18.2 SCA1 8 14.5 Pinto 2021 Brazil 864 DRPLA 8 0.9 42.75 37.5 High Velazquez Perez 2009 Cuba 666 SCA2 578 86.8 33 Moderate MJD/SCA3 8 1.2 Velazquez Perez 2020 Cuba 970 SCA2 848 87.4 37.5 Moderate MJD/SCA3 20 2.1 43.9 SCA7 9 0.9 31.7 Zeigelboim 2015 Brazil 43 MJD/SCA3 12 27.9 41.6 39.5 High SCA2 8 18.6 SCA10 6 14 Studies included in the Systematic Review only Linhares 2006 Brazil 577 SCA7 118 NA 33.3 46.6 Avila Jaque 2024 Mexico 1 SCA19 1 NA Chile 5 SCA19 5 NA Garcia-Velasquez 2013 Mexico 66 SCA7 66 NA Sena 2024 Uruguay 120 SCA2 120 NA Peru Brazil Duggirala 2023 Argentina 3 SCA14 3 NA Baizabal-Carvallo 2015 Bolivia 3 SCA10/SCA2 2 NA 50 SCA10 1 NA 0 Leiva 2022 Colombia 1 SCA10 1 NA 58 100 Carrera-González 2017 Ecuador 2 SCA2 2 NA 0 Abbr.: SCA, spinocerebellar ataxia; GRADE, Grading of Recommendations, Assessment, Development and Evaluation; MJD/SCA3, Machado-Joseph Disease/spinocerebellar ataxia type 3; DRPLA, Dentatorubral-Pallidoluysian Atrophy. Table 2. Main Clusters of SCAs in Latin America. Region (Country) SCAs Highest Reported Frequency (%) Holguin (Cuba) SCA2 86.8 [69] Southern Brazil (Brazil) MJD/SCA3 75.3 [24,25,70] Lara and Yaracuy (Venezuela) SCA7 29.4 [40] Veracruz (Mexico) SCA7 85.9 [43] SCA, spinocerebellar ataxia; MJD, Machado-Joseph Disease. Additional Declarations The authors declare no competing interests. Supplementary Files Supplementarymaterialv2.3MGC.docx Suplementary Material Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5946715","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":410157265,"identity":"719c3e20-f2a2-4219-b394-1eeb6411b3a6","order_by":0,"name":"Milagros Galecio-Castillo","email":"","orcid":"https://orcid.org/0000-0002-8107-9632","institution":"Universidad Cientifica del Sur / University of Iowa Hospital and Clinics","correspondingAuthor":false,"prefix":"","firstName":"Milagros","middleName":"","lastName":"Galecio-Castillo","suffix":""},{"id":410157847,"identity":"2085e79b-3625-44db-837b-2576d9980f9c","order_by":1,"name":"Jesus 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16:45:16","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5946715/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5946715/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75516464,"identity":"16a6d784-16ae-4f2d-94cc-afb1dcdb802b","added_by":"auto","created_at":"2025-02-05 11:29:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":265067,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing the pooled distribution of \u003cstrong\u003e(A)\u003c/strong\u003e all participants with genetic diagnosis of SCA, and \u003cstrong\u003e(B)\u003c/strong\u003eparticipants with unknown diagnosis after genetic testing.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5946715/v1/e37fd945d56a973bfa00b8dc.png"},{"id":75516768,"identity":"a2b1137e-30d8-4613-9778-b64b8aeac13a","added_by":"auto","created_at":"2025-02-05 11:37:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":412659,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing the pooled rates of the most frequent SCAs: \u003cstrong\u003e(A)\u003c/strong\u003e SCA3, \u003cstrong\u003e(B)\u003c/strong\u003e SCA2, \u003cstrong\u003e(C)\u003c/strong\u003e SCA10.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5946715/v1/cd41a4a9aaefe364bb0495eb.png"},{"id":75516463,"identity":"19b6c561-f0dc-4c23-bb38-8ee359573e16","added_by":"auto","created_at":"2025-02-05 11:29:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":206706,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGeographic distribution of published studies on Spinocerebellar Ataxias (SCAs) in Latin America.\u003c/strong\u003e Each box details the number of studies conducted and the total cases identified per SCA subtype. Countries are color-coded based on the number of reported cases: dark green indicates the highest number of published studies, light green represents a lower number, and gray denotes the absence of available data. High frequency (50 or more cases); Low Frequency, at least one case.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5946715/v1/6d85b20c3c10f9c76853558f.png"},{"id":75518926,"identity":"8b2fe637-db38-4e8d-8bcb-b5b3416cd66f","added_by":"auto","created_at":"2025-02-05 11:53:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1975845,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5946715/v1/51f19db8-938d-4731-8411-a8685f6c40a6.pdf"},{"id":75516466,"identity":"cf7a4576-6606-47e5-8261-21337aa5dffa","added_by":"auto","created_at":"2025-02-05 11:29:21","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":249919,"visible":true,"origin":"","legend":"\u003cp\u003eSuplementary Material\u003c/p\u003e","description":"","filename":"Supplementarymaterialv2.3MGC.docx","url":"https://assets-eu.researchsquare.com/files/rs-5946715/v1/187f1714bd059b02d031e3cc.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eEpidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic review and Meta-analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant hereditary ataxias characterized by impairments in the coordination of voluntary movements caused by progressive degeneration of the cerebellum and its associated pathways [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. To date, about 50 genetically distinct subtypes have been identified, with largely variable clinical features ranging from pure cerebellar syndromes to more complex forms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEpidemiological studies on SCAs reveal significant geographic and ethnic differences, with variations in prevalence attributable to founder effects, diverse migrations patterns and the occurrence of some clusters of SCAs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Globally, the Spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD/SCA3) is the most commonly reported SCA, followed by SCA2 and SCA6 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], with significant geographical differences. By contrast, in Asia and Europe, other SCAs such as SCA1, SCA12 and SCA31 have been reported with largest frequencies [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A comprehensive review of inherited ataxias in the Pan-American region, published in 2019, highlighted a high prevalence of MJD/SCA3 in Brazil, SCA2 in Cuba, and SCA10 in populations with Amerindian ancestry, including those in Peru, Mexico, and Brazil [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, this review did not include some recently identified SCAs, such as SCA27B [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and SCA4 [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], underscoring the need for updated and expanded research to capture the evolving genetic landscape of inherited ataxias in the region.\u003c/p\u003e \u003cp\u003eDespite significant advances in the study of SCAs, there remains a notable lack of epidemiological research in most Latin American countries. This gap limits our understanding of the current prevalence of SCAs and their regional variations across diverse geographic areas and known clusters. This study aims to systematically review the literature on the epidemiology of SCAs throughout Latin America. By analyzing existing data, we seek to estimate the frequency and geographic distribution of the most common SCAs by country. In addition, we aim to identify regions with limited or no studies, highlighting areas where further epidemiological research is needed.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines (PRISMA) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The study has been registered on PROSPERO with ID number CRD42024473971.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria and study variables\u003c/h2\u003e \u003cp\u003eWe included published studies that (I) were written in any language; (II) directly investigated dominant spinocerebellar ataxias or SCAs in population residing in Latin America, including the Caribbean countries; (III) had one of the following designs: case reports (including isolated cases), case series (\u0026ge;\u0026thinsp;5 participants for the meta-analysis), observational studies, or experimental studies; and (IV) were published from inception to January 2025. We excluded studies that: (I) lack a definitive diagnosis of SCA through genetic testing; (II) other designs such as review articles, conference abstracts, or research proposals; and (III) studies mainly focused on other regions outside of Latin America. The study variables included: (I) demographic characteristics (age, sex, and geographic location); (II) genetic subtype of SCA (e.g. SCA2, MJD/SCA3, SCA6, DRPLA, SCA10); and (III) clinical outcomes, including diagnostic methods and prevalence rates. Unknown genetic diagnosis was considered only if explicitly specified by the authors.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSearch strategy, studies’ review and selection\u003c/h3\u003e\n\u003cp\u003eWe conducted a systematic electronic literature search by entries to PubMed, Scopus, LILACS, SciELO, and Web of Science, through January 2025. No language restrictions were used, and translation was arranged when necessary. To achieve a comprehensive review, we screened the reference list of relevant records as well. The complete search strategies are detailed in the \u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThree independent reviewers (J.G-A., A.A-M. and M.G-C.) screened all identified records and conducted full-text assessment of the pre-selected studies using the web-based application Rayyan (rayyan.qcri.org) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], which systematically detects, and flags suspected duplicate records. The reviewers carried out data extraction using a data collection tool previously designed and cross-checked the extracted data. Disagreements over study selection were solved by a senior reviewer (M.C-O.).\u003c/p\u003e\n\u003ch3\u003eStudy quality and risk of bias assessment\u003c/h3\u003e\n\u003cp\u003eThe studies included in this systematic review were assessed for risk of bias using the tool [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Two independent reviewers (J.G-A. and E.S-C.) conducted the assessments, evaluating ten domains such as study design, population sampling and data collection method. Each domain was rated as either \u0026ldquo;low\u0026rdquo; or \u0026ldquo;high\u0026rdquo; risk. A summary score was then used to classify studies into three categories: Low risk of bias, moderate risk of bias, and high risk of bias. Disagreements between reviewers were resolved through consultation with a third reviewer (M.C-O.).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eFor studies included in the meta-analysis, we pooled the prevalence rates and calculated a weighted overall proportion with 95% CIs. Due to the small number of events and differences in sample size between studies, we used generalized linear mixed models transformations [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. We used fixed- and random-effects models, and calculated prediction intervals for each meta-analysis. Subgroup meta-analyses were conducted with stratification by SCA type when more than two studies reported the data of interest.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHeterogeneity Assessment and Publication bias\u003c/h3\u003e\n\u003cp\u003eHeterogeneity across studies was assessed using the I\u0026sup2; statistic, which measures the percentage of total variability due to between-study heterogeneity. The Tau\u0026sup2; was also calculated to estimate the variance between studies, with a significance level at P\u0026thinsp;\u0026lt;\u0026thinsp;1.0. Due to the limitations of funnel plots for assessing proportion meta-analysis, we evaluated publication bias through Doi Plots and the LFK index [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All statistical analyses were conducted using R Statistical Software (version 4.3.3) and RStudio (R Foundation for Statistical Computing, Vienna, Austria). Figures and illustrations were generated using R Statistical Software and QGIS.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCertainty of evidence synthesis\u003c/h2\u003e \u003cp\u003eFollowing Cochrane recommendations, 2 reviewers (M.G-C. and J.G-A) independently evaluated the quality of the body of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. The GRADEpro online tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://gradepro.org\u003c/span\u003e\u003cspan address=\"http://gradepro.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was employed to facilitate a structured assessment. Evidence was graded as high, moderate, low or very low.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy selection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified 803 records through a systematic research approach. After removing duplicates, we screened 663\u0026nbsp;records and retrieved 39 articles for full-text assessment. In addition, we identified 6 articles through grey literature search (manual search). Of those, a total of 25 studies were included in the systematic review, and 17 in the meta-analysis \u003cstrong\u003e(Supplementary Figure 1)\u003c/strong\u003e. The studies excluded from the meta-analysis were case reports, focused on participants with a specific SCA, overlapped with other studies included in the meta-analysis (in which case we chose the biggest study for the meta-analysis), or reported data of families.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eRisk of bias\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe included studies were assessed for risk of bias using the adapted tool for prevalence studies by Hol et. al [16]. Of the 17 studies analyzed, ten were classified as having high risk of bias, and the remaining seven as moderate risk. Issues related to external validity were common, primarily due to the regional nature of the populations studied, which lacked clear evidence of national representativeness, limiting the generalizability of findings. On the other hand, internal validity issues were associated with insufficient descriptions of the prevalence period, lack of validation of the measurement instruments used, and the absence of clear reporting of the populations included in prevalence calculations. \u003cstrong\u003eSupplementary Table 2\u003c/strong\u003e provides a detailed assessment of the risk of bias for each included study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudies’ characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive characteristics of the 25 included studies are displayed in \u003cstrong\u003eTable 1\u003c/strong\u003e. They provided data from 5,526 ataxic cases from eleven countries: Brazil (9), Mexico (4), Peru (3), Chile (2), Argentina (2), Cuba (2), Uruguay (1), Venezuela (1), Colombia (1), and Ecuador (1). Of those, Avila Jaque et al. included participants from both Chile and Mexico, and Sena et al. from Peru, Chile, and Uruguay.\u003c/p\u003e\n\u003cp\u003eThe median age of symptoms onset ranged from 23 to 59.9 years old, and 33.3-60% were women.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMeta-analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 17 studies, the SCA types reported and included in the meta-analysis were MJD/SCA3 (13 studies), SCA2 (13 studies), SCA7 (12 studies), SCA1 (9 studies), SCA10 (8 studies), SCA6 (7 studies), SCA8 (2 studies), DRPLA (3 studies), SCA28 (2 studies), as well as SCA4, SCA5, SCA 17, SCA21, SCA27, SCA27b, SCA31, SCA36, SCA42, SCA48, and (1 study each).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 17 studies reported data of 3,880 ataxic cases. The diagnosis index was 61% (95% CI 31-84%), and 39% (95% CI 16-69%) remained as an unknown genetic diagnosis at the time the studies took place \u003cstrong\u003e(Figure 1)\u003c/strong\u003e. When stratifying by type of SCA among all confirmed cases, we found that the most common SCAs in Latin America were MJD/SCA3 (34%, 95% CI 14-62%), and SCA2 (30%, 95% CI 11-59%), followed by SCA10 (9%, 95% CI 3-24%) and SCA7 (9%, 95% CI 4-20%). Other reported SCAs included SCA1 (4%, 95% CI 2-10%), DRPLA (4%, 95% CI 2-6%), and SCA 6 (3%, 2-5%). \u003cstrong\u003e(Figure 2)\u003c/strong\u003e. Regarding SCA distribution by country of origin, we found that SCA2 was most frequently reported in Cuba, MJD/SCA3 in Brazil, Argentina and Mexico, and SCA10 in Peru. \u0026nbsp;\u003cstrong\u003e(Figure 3)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCertainty of evidence\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCertainty of the evidence was low or very low for all the meta-analyses. These results are mainly driven by a moderate-high risk of bias found in all the studies and further downgraded by the design of our work and all the included studies \u003cstrong\u003e(Supplementary Table 3).\u0026nbsp;\u003c/strong\u003eIn addition, large confidence interval found in the random effect models influenced the certainty of evidence results; although we could have excluded studies where a very low rate was reported, most likely due to lack of access to genetic testing, the authors decided to include them in the meta-analyses to ensure that our study reflects the current state of the available literature.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eWe conducted a systematic review and meta-analysis aiming to estimate the frequency and geographic distribution of dominant spinocerebellar ataxias or SCAs in the Latin American region. Our results suggested that SCA2, MJD/SCA3, SCA10, SCA7, and SCA1 are the most prevalent SCAs, with significant geographical variations across and within countries. Importantly, we could not include nor one published study in 22 countries of the Latin American region, \u0026nbsp;presumably related to challenges \u0026nbsp;on diagnostic procedures, lack of access to specialized care, \u0026nbsp;scarce local researchers in the field, scientific papers published in local non-indexed journals, overwhelming work for clinicians preventing them to actively participant in research, funding limitations and language barriers, among others [21\u0026ndash;23].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMJD/SCA3.\u0026nbsp;\u003c/strong\u003eOur results showed that MJD/SCA3 is the most frequent SCA reported in Latin America (34% of pooled cases), with significant variations by regions. Brazil, mainly the southern region, reported a large prevalence of MJD/SCA3 in Latin America, representing 45-73%\u0026nbsp;of all identified SCAs in this region\u0026nbsp;[24,25].\u0026nbsp;MJD/SCA3 was originally reported in three families from the Portuguese Azores islands, and Asian populations\u0026nbsp;[26], \u0026nbsp; this disease which later spread through migrations to Europe, United States and southern Brazil over the last centuries\u0026nbsp;[27]. Haplotype studies performed in the MJD/SCA3 Brazilian cases, identified ancestral mutation within both Machado and Joseph lineage tracing its origin to Portugal and Asia\u0026nbsp;[28]. MJD/SCA3 was also reported in Cuba, Chile, Venezuela, Mexico, Argentina and Peru. Countries with almost no history of Portuguese colonization, like Peru reported very few MJD/SCA3 cases\u0026nbsp;[29].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCA2.\u003c/strong\u003e A high prevalence of SCA2 has been reported in Latin America becoming the second most frequent SCA in the region. SCA2 is the most common subtype in Cuba, Mexico, and Argentina. Worldwide, SCA2 is the second most common subtype of spinocerebellar ataxia and is widely distributed across Europe, India, and South Korea\u0026nbsp;[6,7]. The Cuban population, with a known \u0026nbsp;African and European ancestry, exhibits the highest reported prevalence of SCA2 worldwide, accounting for about 86% of all identified SCAs\u0026nbsp;[8].\u0026nbsp;[26]. The Holguin region in Cuba hosts a well-documented cluster for SCA2, where prevalence reaches 154.3 per 100,000 inhabitants. This clustering has been attributed to a strong founder effect, likely introduced during Spanish colonization, combined with high rates of endogamy. Haplotype studies confirm genetic similarities between Cuban and Spanish populations, supporting this historical connection\u0026nbsp;[26]. SCA2 is also highly prevalent in Mexico and Argentina, likely influenced by Spanish ancestry and potential founder effects coming from Europe\u0026nbsp;[31,32]. In Peru, SCA2 represents the second most commonly diagnosed SCA, possibly reflecting the influence of the Spanish European colonizers, as well as some other migration patterns from non-Hispanic Europeans [23]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCA10\u003c/strong\u003e. \u0026nbsp;Our review identified approximately 7% of all the Latin American SCA cases corresponds to SCA10, being reported as the most prevalent SCA in Peru, and about the top two in Mexico and Brazil, consistent with the known association of SCA10 with Native American ancestry [33]. Haplotype studies have revealed a shared ancestor from both East Asia and the Americas, suggesting that the pathogenic expanded ATTCT tract may have occurred before the divergence of proto-Amerindian populations\u0026nbsp;[26]). In the southern region of Brazil, including Paran\u0026aacute; and Santa Carina \u0026ndash;(the gathering of SCA10 in Brazil)- the SCA10 cases exhibit a pure cerebellar ataxia\u0026nbsp;[34], whereas Mexican phenotype includes seizures\u0026nbsp;[35]. In Peru, the high frequency of SCA10 could be associated with the high Native American ancestry (above 50% on average)\u0026nbsp;[36]. We identified a Bolivian family with SCA10, with at least 2 affected family members also harbor an ATXN2 expansion\u0026nbsp;[37]. No other representative cohorts have been described in Latin American, other SCA10 families have been reported in Bolivia\u0026nbsp;[37], Argentina\u0026nbsp;[38], Colombia\u0026nbsp;[39]\u0026nbsp;and Venezuela\u0026nbsp;[40].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCA7.\u0026nbsp;\u003c/strong\u003eOverall SCA7 represents 7% of all SCA cases in Latin America.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWe found that SCA7 is the most frequent form of SCA in Venezuela and has also been reported with high frequency in Brazil and southeastern Mexico, with lower frequencies in Peru, Argentina and Cuba. Haplotype based studies performed in the two SCA7 clusters in Venezuela, \u0026nbsp;were caused by founder effect (Paradisi et al., 2016). \u0026nbsp; Several studies suggested that migrations patterns and founder effects coming from Europe and South Africa could explain the \u0026nbsp;high relative frequencies of SCA7 [6,40,41]. More than 60% of the SCA7 families in Brazil derived \u0026nbsp;from a region on Northeastern Brazil, where a high inbreeding level was reported\u0026nbsp;[42]. In Veracruz (southeastern Mexico), SCA7 has a documented cluster with \u0026nbsp; an estimated prevalence of 423 per 100,000 inhabitants, likely explained by founder effects linked to Basque and French ancestry\u0026nbsp;[26,43,44].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSCA1\u003c/strong\u003e accounts for 4% of SCAs in Latin America. Most of cases reside in Brazil, Venezuela, Argentina, with rarely and isolated families in Cuba and Peru.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWorldwide SCA1 is mostly prevalent in Poland, Serbia, Russia and Northen Italy [45,45\u0026ndash;48]. Ancestor markers analysis in SCA1 suggest suggests a founder effect in Central Poland [49]. The occurrence of SCA1 in Latin American countries may be mostly related to migration phenomenon, there are no specific clusters or regions in significantly higher frequencies of SCA1.\u003cstrong\u003e\u0026nbsp;SCA6\u0026nbsp;\u003c/strong\u003ehas a low frequency in Latin America, accounting for 2% of all diagnosed SCAs, being mostly reported in Brazil, Argentina and Peru.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eMany SCA6 cases comes from extended family clinical characterizations, with frequency history of Asian ancestors. The typical very late onset of SCA6, together with absence of family history, may increase the risk of misdiagnosis of SCA6\u0026nbsp;[50].\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDentatorubropallidoluysian ataxia or \u003cstrong\u003eDRPLA\u0026nbsp;\u003c/strong\u003eis highly prevalent among Japanese population and in is rarely found in non-Japanese pedigrees with cases described in North America and Europe\u0026nbsp;[51,52]. We identified only 10 cases affected wit, about 8 come from Brazil, with the majority of them declaring a Japanese ancestry. Interestingly, in Venezuela, 2 cases were reported with large family history of apparent just \u0026nbsp;Venezuelan ancestry\u0026nbsp;[40]. By contrast, other countries like Peru, also harboring a large Japanese community, do not identify DRPLA cases. We cannot exclude that fact of underdiagnosis component in DRPLA, as in other countries in the region\u0026nbsp;[53].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecently identified SCAs.\u003c/strong\u003e SCA27B is recently(2022) identified dominant ataxia caused by an intronic GAA repeat expansion within the \u003cem\u003eFGF14\u0026nbsp;\u003c/em\u003egene\u0026nbsp;[9,10]. Recent studies in European and Asian populations have suggested that SCA27b might be one of the most common autosomal dominant ataxias. Worldwide, SCA27B has relative frequencies almost similar to common SCAs such as SCA3/MJD, SCA1, SCA6, and SCA2 in Franco-Canadian [10], Australian [9], German\u0026nbsp;[54], French\u0026nbsp;[55], Spanish\u0026nbsp;[56]\u0026nbsp;cohorts. In Brazil, SCA27B was recently identified as part of the expanding spectrum of genetic causes for late-onset ataxia\u0026nbsp;[57]. Among the nine Brazilian SCA27b, the majority of them were of European descent, consistent with the hypothesis of a European origin for this disease\u0026nbsp;[10,37,44]. A non-consanguineous ataxia family was reported in Chile, in which FGF14 genetic analysis revealed an expanded allele with non-GAA motifs, that currently are considered non-pathogenic \u0026nbsp;[9,10,58,59]. Despite the locus linked to SCA4 was reported back in 1996\u0026nbsp;[60], the GGC-repeat expansion in the ZFHX3 gene was recently (2023) identified by two groups in Sweden and Germany\u0026nbsp;[61\u0026ndash;64]. To date there is only one SCA4 case report identified in Brazil\u0026nbsp;[13]. \u0026nbsp;We found one Brazilian publication reporting 2 cases with SCA45, however the origin of each patient is not specified in the manuscript\u0026nbsp;[65]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrength and limitations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of our review highlight both strengths and critical gaps related to the applied methodology and the limited availability of published studies on SCAs in Latin America. Our systematic approach provides updated epidemiological insights, including data on recently identified SCAs such as SCA27b and SCA4. However, due to insufficient epidemiological data, we were unable to estimate prevalence rates for each country. Additionally, we acknowledge several challenges: variations in sample sizes, inconsistent access to genetic testing (making it difficult to rule out other autosomal dominant SCAs), and a general lack of published or updated data across most countries. Furthermore, potential unidentified overlaps among studies could influence results. To mitigate this, we focused on evaluating percentages rather than absolute numbers to provide a more standardized comparison. The absence of data from several Latin American countries and inconsistent access to genetic testing limits the broader understanding of SCAs in the region. Furthermore, methodological limitations in many studies, emphasize the need for standardize, multicentric research to establish national and continental prevalence rates. Due to inclusion criteria used for this systematic review we excluded cases residing outside Latin America as well as cases harboring more than one SCA mutation; reports of one American case of Colombian origin harboring ATXN10 and HTT expansion [66], and two German siblings of Colombian origin with SCA21 [67], 1 American family of Guatemalan origin with SCA10 [68]. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion or summary","content":"\u003cp\u003eIn conclusion, our study provides a comprehensive analysis of the distribution and frequency of SCAs in Latin America. We identified MJD/SCA3, SCA2, SCA10, and SCA7 as the most prevalent SCAs in the region, with significant geographical variations both within and between countries. Our findings underscore the impact of historical, migratory, and genetic factors on the distribution of these diseases, as evidenced by founder effects in known clusters in the region. Moreover, our study highlights the strong association between specific ancestries and some SCAs, as occurred in SCA10 with consistent frequencies related to the Amerindian ancestry component. To date, recently identified SCAs, such as SCA27B and SCA4 were only reported in Brazil.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the conception of the study. M.G-C., J.G-A and A.A-M performed the literature search and data analysis. The first draft of the manuscript was written by M.G-C and J-G-A. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflicts of interest regarding the present study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was performed with academic support from Universidad Cientifica del Sur and logistic support of Instituto Nacional de Ciencias Neurologicas. The authors would like to thank Mahmoud Dibas (Neurology, University of Iowa Health Care, USA) for his support with conceptualization of the study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eScott SS de O, Pedroso JL, Barsottini OGP, Fran\u0026ccedil;a-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: Insights from the first description to nowadays. J Neurol Sci [Internet]. 2020 [cited 2025 Jan 28];417. Available from: https://www.jns-journal.com/article/S0022-510X(20)30419-6/abstract\u003c/li\u003e\n\u003cli\u003eSullivan R, Yau WY, O\u0026rsquo;Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266:533\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eLima M, Raposo M, Ferreira A, Melo ARV, Pav\u0026atilde;o S, Medeiros F, et al. The Homogeneous Azorean Machado-Joseph Disease Cohort: Characterization and Contributions to Advances in Research. Biomedicines. 2023;11:247. \u003c/li\u003e\n\u003cli\u003eThe Homogeneous Azorean Machado-Joseph Disease Cohort: Characterization and Contributions to Advances in Research [Internet]. [cited 2025 Jan 28]. Available from: https://www.mdpi.com/2227-9059/11/2/247\u003c/li\u003e\n\u003cli\u003eScott SS de O, Pedroso JL, Barsottini OGP, Fran\u0026ccedil;a-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: Insights from the first description to nowadays. J Neurol Sci [Internet]. 2020 [cited 2025 Jan 30];417. Available from: https://www.jns-journal.com/article/S0022-510X(20)30419-6/abstract\u003c/li\u003e\n\u003cli\u003eDe Mattei F, Ferrandes F, Gallone S, Canosa A, Calvo A, Chi\u0026ograve; A, et al. Epidemiology of Spinocerebellar Ataxias in Europe. The Cerebellum. 2024;23:1176\u0026ndash;83. \u003c/li\u003e\n\u003cli\u003eProoije T van, Ibrahim NM, Azmin S, Warrenburg B van de. Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management. 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Mov Disord. 2023;38:1557\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eM\u0026eacute;reaux J-L, Davoine C-S, Pellerin D, Coarelli G, Coutelier M, Ewenczyk C, et al. Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions. eBioMedicine [Internet]. 2024 [cited 2025 Jan 29];99. Available from: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00497-8/fulltext\u003c/li\u003e\n\u003cli\u003eIruzubieta P, Pellerin D, Bergareche A, Albajar I, Mondrag\u0026oacute;n E, Vinagre A, et al. Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia. Eur J Neurol. 2023;30:3828\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eNovis LE, Frezatti RS, Pellerin D, Tomaselli PJ, Alavi S, Della Coleta MV, et al. Frequency of GAA-FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia. 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Am J Hum Genet. 1996;59:392\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eWallenius J, Kafantari E, Jhaveri E, Gorcenco S, Ameur A, Karremo C, et al. Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease. Am J Hum Genet. 2024;111:82\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eChen Z, Gustavsson EK, Macpherson H, Anderson C, Clarkson C, Rocca C, et al. Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in Associated with Spinocerebellar Ataxia Type 4. Mov Disord. 2024;39:486\u0026ndash;97. \u003c/li\u003e\n\u003cli\u003ePaucar M, Nilsson D, Engvall M, Laffita-Mesa J, S\u0026ouml;derh\u0026auml;ll C, Skorpil M, et al. Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs. J Intern Med. 2024;296:234\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eFigueroa KP, Gross C, Buena-Atienza E, Paul S, Gandelman M, Kakar N, et al. A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Nat Genet. 2024;56:1080\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eTonholo Silva TY, Rosa ABR, Quaio CR, Verbeek D, Pedroso JL, Barsottini O. Does SCA45 Cause Very Late-Onset Pure Cerebellar Ataxia? Neurol Genet. 2021;7:e581. \u003c/li\u003e\n\u003cli\u003eRoxburgh RH, Smith CO, Lim JG, Bachman DF, Byrd E, Bird TD. The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease. J Neurol Sci. 2013;324:176\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eTrasch\u0026uuml;tz A, Gaalen J van, Oosterloo M, Vreeburg M, Kamsteeg E-J, Deininger N, et al. The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature. Parkinsonism Relat Disord. 2019;62:215\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eTrikamji B, Singh P, Mishra S. Spinocerebellar ataxia-10 with paranoid schizophrenia. Ann Indian Acad Neurol. 2015;18:93. \u003c/li\u003e\n\u003cli\u003eVel\u0026aacute;zquez-P\u0026eacute;rez L, Medrano-Montero J, Rodr\u0026iacute;guez-Labrada R, Canales-Ochoa N, Campins Al\u0026iacute; J, Carrillo Rodes FJ, et al. Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients. The Cerebellum. 2020;19:252\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003ede Castilhos RM, Furtado GV, Gheno TC, Schaeffer P, Russo A, Barsottini O, et al. Spinocerebellar Ataxias in Brazil\u0026mdash;Frequencies and Modulating Effects of Related Genes. The Cerebellum. 2014;13:17\u0026ndash;28. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e Summary of the studies included in the systematic review and meta-analysis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParticipants (N)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCA types\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCA (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCA (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian age at onset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWomen (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk of bias\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudies included in the Systematic Review and Meta-analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlonso 2007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 57px;\"\u003e\n \u003cp\u003eMexico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 61px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e45.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlvarenga 2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e69.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e40.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e54.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCornejo-Olivas 2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePeru\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e48.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCornejo-Olivas 2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003ePeru\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e46.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ede Castilhos 2014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e59.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e29.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaga\u0026ntilde;a 2014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003eMexico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e85.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e32.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMassuyama 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e51.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e60\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e18.3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e39\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e11.9\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMiranda 2015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eChile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMoraes 2023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e75.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e37.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e54.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e15.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e25.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNascimiento 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e47.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e53.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNovis 2023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA27B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e59.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e44.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParadisi 2016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 57px;\"\u003e\n \u003cp\u003eVenezuela\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 61px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e29.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e30.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e21.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e27.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e41.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerez Maturo 2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eArgentina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e36.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 74px;\"\u003e\n \u003cp\u003e30.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e54.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePinto 2021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e864\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eDRPLA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e42.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVelazquez Perez 2009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003eCuba\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e578\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e86.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVelazquez Perez 2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eCuba\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e970\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e87.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e43.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e31.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZeigelboim 2015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 74px;\"\u003e\n \u003cp\u003e41.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e39.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudies included in the Systematic Review only\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLinhares 2006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e46.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAvila Jaque 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eMexico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eChile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGarcia-Velasquez 2013\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eMexico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSena 2024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUruguay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 61px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 41px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 41px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003ePeru\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuggirala 2023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eArgentina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eSCA14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003eNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaizabal-Carvallo 2015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003eBolivia\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA10/SCA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003eNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e50\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003eNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLeiva 2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003eColombia\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003eNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cem\u003e58\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e100\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarrera-Gonz\u0026aacute;lez 2017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003eEcuador\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eSCA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cem\u003eNA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003eAbbr.: SCA, spinocerebellar ataxia; GRADE, Grading of Recommendations, Assessment, Development and Evaluation; MJD/SCA3, Machado-Joseph Disease/spinocerebellar ataxia type 3; DRPLA, Dentatorubral-Pallidoluysian Atrophy.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eMain Clusters of SCAs in Latin America.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"619\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 294px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion (Country)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCAs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 188px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHighest Reported Frequency (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 294px;\"\u003e\n \u003cp\u003eHolguin (Cuba)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eSCA2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 188px;\"\u003e\n \u003cp\u003e86.8 [69]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 294px;\"\u003e\n \u003cp\u003eSouthern Brazil (Brazil)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eMJD/SCA3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 188px;\"\u003e\n \u003cp\u003e75.3 [24,25,70]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 294px;\"\u003e\n \u003cp\u003eLara and Yaracuy (Venezuela)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 188px;\"\u003e\n \u003cp\u003e29.4 [40]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 294px;\"\u003e\n \u003cp\u003eVeracruz (Mexico)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eSCA7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 188px;\"\u003e\n \u003cp\u003e85.9 [43]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSCA, spinocerebellar ataxia; MJD, Machado-Joseph Disease.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Universidad Cientifica del Sur","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"SCA, Spinocerebellar ataxia, epidemiology, Latin America, systematic review, meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-5946715/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5946715/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant neurodegenerative disorders characterized by progressive cerebellar ataxia, affecting motor coordination. SCAs are reported globally with large geographical and ethnic differences. This systematic review and meta-analysis aimed to update the frequency, and geographic distribution of SCAs in Latin America, including recently identified SCAs like SCA27b. We conducted a systematic search in PubMed, Scopus, LILACS, SciELO and Web of Science databases, including studies published from inception to January 2025. We included 25 studies for the systematic review and 17 studies for the meta-analysis that met the inclusion criteria, representing a total of 5,546 participants across eleven countries. Our meta-analysis revealed that about 61% (95% CI 31\u0026ndash;84%) of hereditary ataxias in Latin America were confirmed to have a genetic diagnosis of SCA. The included participants with a known SCA have the following proportions: MJD/SCA3 (34%), SCA2 (30%), SCA10 (9%), SCA7 (9%) and SCA1 (4%). Geographic distributions were notable, MJD/SCA3 in Brazil, SCA2 in Cuba, Argentina and Mexico, SCA10 predominating in Peru, and SCA7 in Venezuela. Recently identified subtypes, like SCA27B and one case of SCA4, were identified in Brazil. In 22 countries there are no published studies on the epidemiology of SCAs. The distribution of SCAs in Latin America reflects the influence of historical migrations, founder effects, and ancestries, emphasizing regional heterogeneity. Our findings underscore the critical need for further epidemiological studies, particularly in understudied countries in the region.\u003c/p\u003e","manuscriptTitle":"Epidemiology of Autosomal Dominant Spinocerebellar Ataxias in Latin America: A Systematic review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-05 11:29:16","doi":"10.21203/rs.3.rs-5946715/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7b18bda2-6607-47df-829a-c42182ca3974","owner":[],"postedDate":"February 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":43730684,"name":"Molecular Epidemiology"},{"id":43730685,"name":"Medical Genetics"},{"id":43730686,"name":"Neurology"},{"id":43730687,"name":"Epidemiology"},{"id":43730688,"name":"Statistical Epidemiology"}],"tags":[],"updatedAt":"2025-02-05T11:29:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-05 11:29:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5946715","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5946715","identity":"rs-5946715","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}