Ana Saldarriaga-Mayo

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.

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 hereditarias representan un grupo diverso de enfermedades neurogenéticas caracterizadas por alteraciones en la coordinación motora, debido a la disfunción del cerebelo o sus vías asociadas. Estas enfermedades incluyen formas autosómicas dominantes, recesivas, ligadas al cromosoma X y mitocondriales. El diagnóstico y el tratamiento son complejos, más aún en regiones con recursos limitados como Perú y otros países de Latinoamérica, donde se presentan desafíos adicionales. Esta revisión propone un enfoque diagnóstico estructurado para las ataxias hereditarias que consiste en cinco ejes: 1) confirmación del tipo de ataxia (cerebelosa o no cerebelosa); 2) edad de inicio; 3) forma de presentación (predominantemente pura o plus); 4) historia familiar; y 5) exclusión de causas reversibles o secundarias. Los estudios auxiliares más útiles en el diagnóstico diferencial, dependiendo de la información recolectada de los 5 ejes, incluyen análisis séricos, neuroimagen, estudios neurofisiológicos, evaluaciones neurooftalmológicas, pruebas vestibulares y estudios genéticos (genes específicos, paneles genéticos, exoma y genoma clínico). La implementación de un enfoque diagnóstico basado en estos pilares optimiza tanto el diagnóstico como el manejo clínico de esta enfermedad, especialmente en contextos con recursos limitados.

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.