Spinocerebellar Ataxia Type 23 (SCA23): a rare cause of SCA in the Americas

Spinocerebellar Ataxia Type 23 (SCA23): a rare cause of SCA in the Americas | 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 Case Report Spinocerebellar Ataxia Type 23 (SCA23): a rare cause of SCA in the Americas Victor Monteiro Dias Saadeh, Daniel Nassif, Luiz Felipe Vasconcellos This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8167444/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Apr, 2026 Read the published version in The Cerebellum → Version 1 posted 7 You are reading this latest preprint version Abstract Spinocerebellar ataxia type 23 (SCA23) is a rare autosomal dominant hereditary ataxia caused by mutation in the PDYN gene. It usually presents in adulthood, with a mean age of onset around 43 years, and progresses slowly with cerebellar symptoms. We report a case of a Brazilian 25-year-old female patient whose symptoms began at 19 years of age, characterized by progressive dysarthria, tremor, dysphagia, and gait disturbance. She had no relatives with similar symptoms. The initial genetic ataxia panel, which included the most prevalent hereditary ataxia genes, was negative. Subsequent next-generation sequencing identified a pathogenic PDYN mutation, confirming the diagnosis of SCA23. Brain MRI demonstrated significant cerebellar atrophy. The patient was referred to a multidisciplinary rehabilitation group with emphasis on functional rehabilitation of gait and dysphagia. This case is notable due to the rarity of this SCA in the Americas, as well for its early onset, given the mean age of SCA23 in the literature, and for the lack of family history of ataxia or any neurological symptoms, suggesting a de novo mutation. Movement Disorders Neurogenetics Hereditary ataxia Spinocerebellar ataxia Magnetic Resonance Imaging Figures Figure 1 Introduction Spinocerebellar ataxias (SCAs) are a heterogeneous group of genetic neurodegenerative disorders characterized by progressive cerebellar ataxia. They are autosomal dominant conditions, with more than 50 subtypes identified to date. 1 Although genetic ataxias are considered rare, in specialized centers, they could represent 33% of all ataxic patients. 2 The most prevalent SCAs in Brazil, also in Latin America, are SCA3, followed by SCA7 and SCA2, which is consistent with the distribution patterns reported worldwide. 3 SCA23 was first described in 2004, when Verbeek et al. reported a Dutch family affected over three generations, identifying a pathogenic locus on chromosome region 20p13-12.3 through linkage analysis. 4 Later, in 2010, Bakalkin et al. identified the PDYN gene as the pathogenic gene responsible for SCA23. 5 Also, Saigoh et al. described the first case in Japan, Liu et al. reported a case in China, Pedroso et al in Brazil, and Fogel et al in the United States. 6 , 7 , 8 , 9 Therefore, SCA23 is rarely described, with this report being the third in the Americas and the second in Brazil. Case Report This is a descriptive and exploratory case study of a Brazilian 25-year-old female patient. The patient’s symptoms began at 19 years of age, with progressive dysarthria, rest and action asymmetric tremor of the upper limbs, and handwriting difficulty. By the age of 21, she developed ataxic gait, with frequent falls requiring assistance to walk, and dysphagia. The exam revealed cerebellar dysarthria, gait ataxia, hypotonia, dysmetria, universal areflexia, and central nystagmus, with hypermetric saccades. The patient denied any family history of similar symptoms or consanguinity. Brain magnetic resonance imaging (MRI) revealed significant atrophy of the cerebellum (Fig. 1). Genetic testing for SCA types 1, 2, 3, 6, 7, 8, and 10, as well as Friedreich’s ataxia and fragile X, were all negative. Acquired and treatable causes, such as toxic, nutritional, or paraneoplastic etiologies, were also excluded. An expanded ataxia panel identified a pathogenic heterozygous variant in the PDYN gene, c.144G > T (p.Arg138Ser), confirming the diagnosis of SCA23. The patient currently receives multidisciplinary follow-up, including physical, speech, occupational, and equine therapy. Figure 1 – Sagittal T1-weighted image showing pronounced cerebellar atrophy, with preservation of supratentorial structures. Discussion The SCA23 is characterized by gait ataxia, limb ataxia, dysarthria, and hyperreflexia, with gait ataxia being the most common initial symptom. Other possible symptoms include oculomotor impairment or saccade slowing, Babinski’s sign, tremor, and polyneuropathy. However, no specific clinical findings are able to distinguish between SCA23 from other SCAs. 10 It typically presents in middle-aged adults, with a mean onset of 43 ± 15 years. However, in the present case, symptom onset occurred at 19 years old, being an early-onset phenotype. A de novo or functionally more deleterious mutation, possibly influenced by individual genetic or epigenetic modifiers, may explain the unusually early onset observed in this case. 5 , 9 , 10 Reported prevalence is low: in cohort studies of ataxia patients, SCA23 accounted for 0.36–1.08% of cases. 6 , 7 , 10 This report represents the third case of SCA23 in Western countries, which, in addition to the rarity of this condition, could also be related to the limited inclusion of the PDYN gene in routine genetic panels for patients who test negative for the most common SCAs subtypes. 8 , 9 Neuroimaging, particularly MRI, can reveal abnormalities even before clinical symptoms appear, aiding early diagnosis. The most common finding in SCA23 is cerebellar atrophy, involving the cerebellar cortex, middle cerebellar peduncles, cerebral cortex, and corpus callosum. 10 In our patient, brain MRI revealed severe cerebellar atrophy as the primary radiological abnormality. SCA23 is a progressive and incurable neurodegenerative disorder, typically autosomal dominant. There was no family history in the present case, suggesting a de novo mutation, which refers to a genetic alteration that arises spontaneously in an individual and is not inherited from either parent. A similar finding was previously described by Fogel et al., who reported the only known case of SCA23 associated with a de novo pathogenic variant. 9 Although progression is usually slow, patients may develop significant motor disability over time. 11 This underscores the importance of multidisciplinary care — including physical, occupational, and speech therapy — alongside regular neurologic follow-up with specialists. Conclusion SCA23 is a rare cause of adult-onset hereditary ataxia, typically affecting middle-aged individuals. Its true prevalence may be underestimated, given the limited availability of expanded genetic panels that include PDYN. In the present case, the early onset of symptoms and the absence of familial history are noteworthy, expanding the recognized clinical spectrum of SCA23. Although genetic anticipation can occur in other SCAs, there were no similar cases in the family, suggesting this is likely a de novo mutation. This report emphasizes the importance of comprehensive genetic testing in atypical or early-onset cases of ataxia, as well as continued multidisciplinary follow-up and systematic case documentation to improve understanding of the genotypic and phenotypic variability of SCA23. Declarations Conflict of interest: The authors declare no conflict of interest. Funding: The authors received no financial support for this research. Consent for Publication: Written informed consent was obtained from the patient. Authors’ Contributions: VMDS drafted the manuscript, LFV and DN concept and design, major data acquisition, supervised, and critically revised the content All authors reviewed and approved the final version of the manuscript. References Zesiewicz TA. Ataxia. Continuum (Minneap Minn). 2025;31(4):1093–1119. doi: 10.1212/cont.0000000000001599. Epub 2025 Aug 1. PMID: 40748127. Pellerin D, Iruzubieta P, Xu IRL, et al. Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions. Curr Neurol Neurosci Rep. 2025;25:16. 10.1007/s11910-024-01400-8 . Ganimi MCC, Couto CM, Ferreira ALR, Paiva CLA. Spinocerebellar Ataxia in Brazil: A Comprehensive Genotype–Phenotype Analysis. Cerebellum. 2024;23:2414–25. 10.1007/s12311-024-01745-3 . Verbeek DS, van de Warrenburg BP, Wesseling P, Pearson PL, Kremer HP, Sinke RJ. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13–12.3. Brain. 2004;127(11):2551–7. 10.1093/brain/awh276 . Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren-Bemelmans C, Bazov I, et al. Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet. 2010;87(5):593–603. 10.1016/j.ajhg.2010.10.001 . Saigoh K, Mitsui J, Hirano M, Shioyama M, Samukawa M, Ichikawa Y, et al. The first Japanese familial case of spinocerebellar ataxia 23 with a novel mutation in the PDYN gene. Parkinsonism Relat Disord. 2015;21(3):332–4. 10.1016/j.parkreldis.2014.12.028 . Liu YT, Tang BS, Wang JL, Guan WJ, Shen L, Shi YT, et al. Spinocerebellar ataxia type 23 is an uncommon SCA subtype in the Chinese Han population. Neurosci Lett. 2012;528:51–4. 10.1016/j.neulet.2012.08.062 . Pedroso JL, Vale TC, Freua F, Barsottini OGP, Kok F. SCA23 and prodynorphin: is it time for gene retraction? Brain. 2016;139(8):e42. 10.1093/brain/aww093 . Fogel BL, Lee JY, Lane J, Wahnich A, Chan S, Huang A, et al. Mutations in rare ataxia genes are uncommon causes of sporadic cerebellar ataxia. Mov Disord. 2012;27(3):442–5. 10.1002/mds.24064 . Wu F, Wang X, Li X, Teng H, Tian T, Bai J. Spinocerebellar ataxia type 23 (SCA23): a review. J Neurol. 2021;268(11):4630–45. 10.1007/s00415-020-10297-5 . Hekman KE, Yu Y, Brown CD, Zhu H, Schelhaas HJ, Lynch DR, et al. Intrafamilial phenotypic variation in spinocerebellar ataxia type 23. Cerebellum Ataxias. 2020;7(5):1–8. 10.1186/s40673-020-00117-1 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Apr, 2026 Read the published version in The Cerebellum → Version 1 posted Editorial decision: Revision requested 17 Jan, 2026 Reviews received at journal 31 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviewers invited by journal 08 Dec, 2025 Editor assigned by journal 20 Nov, 2025 Submission checks completed at journal 20 Nov, 2025 First submitted to journal 20 Nov, 2025 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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1","display":"","copyAsset":false,"role":"figure","size":55580,"visible":true,"origin":"","legend":"\u003cp\u003eSagittal T1-weighted image showing pronounced cerebellar atrophy, with preservation of supratentorial structures.\u003c/p\u003e","description":"","filename":"Fig1.eps.png","url":"https://assets-eu.researchsquare.com/files/rs-8167444/v1/01f131be66ec81ed2f482dea.png"},{"id":107928313,"identity":"dc525f7e-ffbf-4887-bdb6-383391833fd1","added_by":"auto","created_at":"2026-04-27 16:09:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":181905,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8167444/v1/5d7ed806-418c-4fb4-8393-fef6d2e2bcf3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Spinocerebellar Ataxia Type 23 (SCA23): a rare cause of SCA in the Americas","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSpinocerebellar ataxias (SCAs) are a heterogeneous group of genetic neurodegenerative disorders characterized by progressive cerebellar ataxia. They are autosomal dominant conditions, with more than 50 subtypes identified to date.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Although genetic ataxias are considered rare, in specialized centers, they could represent 33% of all ataxic patients.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The most prevalent SCAs in Brazil, also in Latin America, are SCA3, followed by SCA7 and SCA2, which is consistent with the distribution patterns reported worldwide.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e SCA23 was first described in 2004, when Verbeek et al. reported a Dutch family affected over three generations, identifying a pathogenic locus on chromosome region 20p13-12.3 through linkage analysis.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Later, in 2010, Bakalkin et al. identified the PDYN gene as the pathogenic gene responsible for SCA23.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Also, Saigoh et al. described the first case in Japan, Liu et al. reported a case in China, Pedroso et al in Brazil, and Fogel et al in the United States.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Therefore, SCA23 is rarely described, with this report being the third in the Americas and the second in Brazil.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eThis is a descriptive and exploratory case study of a Brazilian 25-year-old female patient. The patient\u0026rsquo;s symptoms began at 19 years of age, with progressive dysarthria, rest and action asymmetric tremor of the upper limbs, and handwriting difficulty. By the age of 21, she developed ataxic gait, with frequent falls requiring assistance to walk, and dysphagia. The exam revealed cerebellar dysarthria, gait ataxia, hypotonia, dysmetria, universal areflexia, and central nystagmus, with hypermetric saccades. The patient denied any family history of similar symptoms or consanguinity.\u003c/p\u003e\u003cp\u003eBrain magnetic resonance imaging (MRI) revealed significant atrophy of the cerebellum (Fig.\u0026nbsp;1).\u003c/p\u003e\u003cp\u003eGenetic testing for SCA types 1, 2, 3, 6, 7, 8, and 10, as well as Friedreich\u0026rsquo;s ataxia and fragile X, were all negative. Acquired and treatable causes, such as toxic, nutritional, or paraneoplastic etiologies, were also excluded. An expanded ataxia panel identified a pathogenic heterozygous variant in the PDYN gene, c.144G\u0026thinsp;\u0026gt;\u0026thinsp;T (p.Arg138Ser), confirming the diagnosis of SCA23.\u003c/p\u003e\u003cp\u003eThe patient currently receives multidisciplinary follow-up, including physical, speech, occupational, and equine therapy.\u003c/p\u003e\u003cp\u003eFigure 1 \u0026ndash; Sagittal T1-weighted image showing pronounced cerebellar atrophy, with preservation of supratentorial structures.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe SCA23 is characterized by gait ataxia, limb ataxia, dysarthria, and hyperreflexia, with gait ataxia being the most common initial symptom. Other possible symptoms include oculomotor impairment or saccade slowing, Babinski\u0026rsquo;s sign, tremor, and polyneuropathy. However, no specific clinical findings are able to distinguish between SCA23 from other SCAs.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e It typically presents in middle-aged adults, with a mean onset of 43\u0026thinsp;\u0026plusmn;\u0026thinsp;15 years. However, in the present case, symptom onset occurred at 19 years old, being an early-onset phenotype. A \u003cem\u003ede novo\u003c/em\u003e or functionally more deleterious mutation, possibly influenced by individual genetic or epigenetic modifiers, may explain the unusually early onset observed in this case.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eReported prevalence is low: in cohort studies of ataxia patients, SCA23 accounted for 0.36\u0026ndash;1.08% of cases.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e This report represents the third case of SCA23 in Western countries, which, in addition to the rarity of this condition, could also be related to the limited inclusion of the PDYN gene in routine genetic panels for patients who test negative for the most common SCAs subtypes.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNeuroimaging, particularly MRI, can reveal abnormalities even before clinical symptoms appear, aiding early diagnosis. The most common finding in SCA23 is cerebellar atrophy, involving the cerebellar cortex, middle cerebellar peduncles, cerebral cortex, and corpus callosum.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e In our patient, brain MRI revealed severe cerebellar atrophy as the primary radiological abnormality.\u003c/p\u003e\u003cp\u003eSCA23 is a progressive and incurable neurodegenerative disorder, typically autosomal dominant. There was no family history in the present case, suggesting a \u003cem\u003ede novo\u003c/em\u003e mutation, which refers to a genetic alteration that arises spontaneously in an individual and is not inherited from either parent. A similar finding was previously described by Fogel et al., who reported the only known case of SCA23 associated with a \u003cem\u003ede novo\u003c/em\u003e pathogenic variant.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Although progression is usually slow, patients may develop significant motor disability over time.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e This underscores the importance of multidisciplinary care \u0026mdash; including physical, occupational, and speech therapy \u0026mdash; alongside regular neurologic follow-up with specialists.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSCA23 is a rare cause of adult-onset hereditary ataxia, typically affecting middle-aged individuals. Its true prevalence may be underestimated, given the limited availability of expanded genetic panels that include PDYN. In the present case, the early onset of symptoms and the absence of familial history are noteworthy, expanding the recognized clinical spectrum of SCA23. Although genetic anticipation can occur in other SCAs, there were no similar cases in the family, suggesting this is likely a de novo mutation. This report emphasizes the importance of comprehensive genetic testing in atypical or early-onset cases of ataxia, as well as continued multidisciplinary follow-up and systematic case documentation to improve understanding of the genotypic and phenotypic variability of SCA23.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interest:\u003cbr\u003e\u0026nbsp;The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding:\u003cbr\u003e\u0026nbsp;The authors received no financial support for this research.\u003c/p\u003e\n\u003cp\u003eConsent for Publication:\u003cbr\u003e\u0026nbsp;Written informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003eAuthors’ Contributions:\u003cbr\u003e\u0026nbsp;VMDS drafted the manuscript, LFV and DN concept and design, major data acquisition, supervised, and critically revised the content All authors reviewed and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZesiewicz TA. 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Cerebellum Ataxias. 2020;7(5):1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s40673-020-00117-1\u003c/span\u003e\u003cspan address=\"10.1186/s40673-020-00117-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Movement Disorders, Neurogenetics, Hereditary ataxia, Spinocerebellar ataxia, Magnetic Resonance Imaging","lastPublishedDoi":"10.21203/rs.3.rs-8167444/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8167444/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSpinocerebellar ataxia type 23 (SCA23) is a rare autosomal dominant hereditary ataxia caused by mutation in the PDYN gene. It usually presents in adulthood, with a mean age of onset around 43 years, and progresses slowly with cerebellar symptoms. We report a case of a Brazilian 25-year-old female patient whose symptoms began at 19 years of age, characterized by progressive dysarthria, tremor, dysphagia, and gait disturbance. She had no relatives with similar symptoms. The initial genetic ataxia panel, which included the most prevalent hereditary ataxia genes, was negative. Subsequent next-generation sequencing identified a pathogenic PDYN mutation, confirming the diagnosis of SCA23. Brain MRI demonstrated significant cerebellar atrophy. The patient was referred to a multidisciplinary rehabilitation group with emphasis on functional rehabilitation of gait and dysphagia. This case is notable due to the rarity of this SCA in the Americas, as well for its early onset, given the mean age of SCA23 in the literature, and for the lack of family history of ataxia or any neurological symptoms, suggesting a \u003cem\u003ede novo\u003c/em\u003e mutation.\u003c/p\u003e","manuscriptTitle":"Spinocerebellar Ataxia Type 23 (SCA23): a rare cause of SCA in the Americas","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-11 09:50:19","doi":"10.21203/rs.3.rs-8167444/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-17T19:33:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-31T10:22:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"269698119039962331061942940345065311029","date":"2025-12-08T21:30:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-08T14:57:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-21T01:18:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-21T01:18:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Cerebellum","date":"2025-11-20T19:12:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"aa625e57-a4b5-4584-bef2-7b7b4693bf17","owner":[],"postedDate":"December 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T16:07:18+00:00","versionOfRecord":{"articleIdentity":"rs-8167444","link":"https://doi.org/10.1007/s12311-026-02001-6","journal":{"identity":"the-cerebellum","isVorOnly":false,"title":"The Cerebellum"},"publishedOn":"2026-04-20 15:59:55","publishedOnDateReadable":"April 20th, 2026"},"versionCreatedAt":"2025-12-11 09:50:19","video":"","vorDoi":"10.1007/s12311-026-02001-6","vorDoiUrl":"https://doi.org/10.1007/s12311-026-02001-6","workflowStages":[]},"version":"v1","identity":"rs-8167444","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8167444","identity":"rs-8167444","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}