Molecular and genetic landscape of amyotrophic lateral sclerosis in Latin America: a scoping review of pathogenic hypotheses and ancestral heterogeneity.

Background

The genetic architecture of amyotrophic lateral sclerosis (ALS) has been predominantly characterized in populations of European ancestry, while Latin American populations remain underrepresented despite their complex admixture.

Objective

To map the molecular hypotheses explored in ALS research conducted in Latin American populations and identify key methodological and structural gaps.

Methods

A scoping review was conducted following Joanna Briggs Institute methodology and reported according to PRISMA-ScR guidelines. Searches were performed in Web of Science, Scopus, PubMed/MEDLINE, SciELO, and LILACS. Studies investigating genetic or molecular aspects of ALS or the ALS-FTD spectrum in Latin American populations were included. Data were extracted using a standardized matrix and synthesized descriptively.

Results

Nineteen studies met inclusion criteria. Most were small, single-center investigations employing targeted candidate-gene approaches, predominantly focused on C9orf72 expansions and SOD1 mutations. Reported C9orf72 frequencies varied substantially across countries, indicating population-specific genetic heterogeneity. Only one study incorporated explicit ancestry inference, and no genome-wide association studies or large multicenter ALS genomic cohorts were identified.

Conclusions

ALS research in Latin America remains limited, fragmented, and largely candidate-gene driven, with minimal integration of ancestry-informed approaches. The absence of large-scale genomic studies, despite existing regional sequencing capacity, highlights the need for coordinated multicenter initiatives to enable equitable implementation of precision medicine.