Alonso Abad

Spinocerebellar ataxia type 27B (SCA27B) is a recently described autosomal dominant ataxia caused by a pathogenic GAA repeat expansion in the FGF14 gene. The frequency and the distribution of FGF14 repeat alleles remain largely unexplored in underrepresented populations, particularly in Latin America. To investigate the frequency of SCA27B and characterize the allelic distribution of the GAA-FGF14 microsatellite locus in a Peruvian cohort of individuals with ataxia of unknown molecular etiology. We analysed a cohort of affected individuals evaluated at a referral center for neurogenetic disorders in Peru. All individuals underwent standardized neurological assessment, as well as molecular analysis of the GAA-FGF14 repeat locus using repeat-primed and long-range PCR-based approaches. One genetically confirmed case of SCA27B was identified, corresponding to a frequency of 0.6% (1/167) in this cohort. Most alleles (91.61%) were within the non-pathogenic range (< 250 repeats), 85.3% of them with less than 30 repeats. Notably, 16.17% of individuals carried non-GAA-pure expanded alleles with a complex [(GAA)_n(GCA)_m]_z repeat structure, currently considered non-pathogenic. These alleles were not associated with a typical SCA27B phenotype. SCA27B appears to be a rare cause of hereditary ataxia in the Peruvian population. The high prevalence of non-GAA-pure expanded alleles and the distinct FGF14 allelic distribution illustrates the allelic diversity of the FGF14 GAA locus. These findings highlight the importance of investigating diverse populations to better understand the genetic mechanisms underlying SCA27B and other repeat expansion-associated ataxias.

Background: Spinocerebellar ataxia type 10 (SCA10 or ATX‐ ATXN10 ) is typically attributed to large intronic ATTCT repeat expansions in ATXN10 , yet interpretation is complicated by repeat interruptions, reduced penetrance, and assay limitations. Cases: We describe three patients referred for SCA10 evaluation in whom ATXN10 repeat‐primed PCR (RP‐PCR) reported “>32 repeats, probable pathogenic.” Targeted long‐read sequencing (LRS) identified two individuals with intermediate, mixed repeat tracts (~100–150 repeats) and one individual with a very large, highly pure ATTCT expansion (~1127 repeats). Each phenotype was explained by an alternative disorder: spastic ataxia syndrome caused by biallelic pathogenic FA2H variants (HSP/ATX‐ FA2H ), full‐penetrance ATXN3 CAG expansion consistent with SCA3/ATX‐ ATXN3 , and clinically established MSA‐C. Literature Review: We identified three studies reporting four ATX‐ ATXN10 cases coexisting with Huntington's disease (one case) and SCA2/ATX‐ ATXN2 (three cases). Conclusion: Our three cases suggest that intermediate ATXN10 alleles in the 100–150 range may not be pathogenic and large ATXN10 expansions remain probably pathogenic in most patients with a compatible autosomal‐dominant ataxia phenotype. Comprehensive genetic testing beyond RP‐PCR is necessary for accurate diagnosis.

Objetivo: Comparar la frecuencia de crisis epilépticas entre pacientes con SCA10 y otras SCA en una muestra de la población peruana. Materiales y métodos: Estudio observacional con componente retrospectivo con revisión de historias clínicas y prospectivo con entrevista previo consentimiento informado. Se reclutaron pacientes con diagnóstico genético de SCA atendidos entre enero de 2014 y diciembre de 2023 en un centro de referencia nacional de Perú. Resultados: Se identificaron 125 casos/87 familias con diagnóstico de seis tipos de SCA (SCA1, SCA2, MJD/SCA3, SCA6, SCA7 y SCA10), con una frecuencia global de 11,2 % de crisis epilépticas. Estas predominaron en el subgrupo SCA10 (16 %), en contraste con el subgrupo de otras SCA (4 %), donde se hallaron dos casos de SCA2 con crisis epilépticas. Conclusiones: Las crisis epilépticas son significativamente más frecuentes en SCA10 respecto de las otras SCA en la población estudiada. Predominan las crisis de inicio desconocido tipo motor tónico-clónicas en SCA10 y las crisis de inicio focales motoras en SCA2, ambas con buena respuesta a medicación anticrisis.

Las ataxias espinocerebelosas (SCAs) son enfermedades degenerativas caracterizadas por incoordinación de origen cerebeloso acompañada de síntomas no motores variables, incluyendo crisis epilépticas. La ataxia espinocerebelosa tipo 10 (SCA10), asocia crisis epilépticas con variaciones geográficas, también halladas en casos de SCA2, SCA6, SCA8, SCA13, SCA17, SCA19/22 y atrofia dentatorubropalidoluisiana (DRPLA). No hay estudios que describan las crisis epilépticas en pacientes con SCAs en la población peruana. Objetivo: Comparar la frecuencia de crisis epilépticas entre pacientes con SCA10 y otras SCAs en una muestra de la población peruana. Materiales y métodos: Estudio observacional con componente retrospectivo con revisión de historias clínicas y prospectivo con entrevista previo consentimiento informado. Se reclutaron pacientes con diagnóstico genético de SCA atendidos entre enero 2014 y diciembre 2023 en un centro de referencia nacional de Perú. Resultados: Identificamos 125 casos/87 familias con diagnóstico de 6 tipos de SCA (SCA1, SCA2, MJD/SCA3, SCA6, SCA7 y SCA10), con una frecuencia global de 11.2 % de crisis epiléptica. Las crisis epilépticas predominan en el subgrupo SCA10 (16%) contrastando con el subgrupo de otras SCAs con solo 2 casos de crisis epilépticas en SCA2 (4%). Conclusiones: Las crisis epilépticas son significativamente más frecuentes en SCA10 respecto de las otras SCAs en la población estudiada. Las crisis tónico-clónico de inicio desconocido o generalizado en SCA10 y las crisis de inicio focales motoras en SCA2 son las predominantes, con buena respuesta a monoterapia de fármacos anticonvulsivantes.

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 27 studies for the systematic review and 18 studies for the meta-analysis that met the inclusion criteria, representing a total of 5859 participants across eleven countries. Our meta-analysis revealed that about 50% (95% CI 26–74%) 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 (15%), SCA2 (11%), SCA7 (4%), SCA10 (3%), and SCA1 (3%). Geographic distributions were notable, MJD/SCA3 in Brazil, SCA2 in Cuba, Argentina and Mexico, SCA10 predominating in Peru, and SCA7 in Venezuela. Recently identified SCA types, 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.

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.