FXTAS and the FMR1 Premutation Phenotypic Spectrum in Latin America: A Scoping Review
Amy Schmidmajer1, Santiago Martinez1, Salomon Páez-García1, Jacobo Ramírez - Triana1, Catalina Cerquera- Cleves2
1Pontificia Universidad Javeriana, 2Neurology, Hospital Universitario San Ignacio
Objective:
To review the available evidence on Fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related phenotypes in Latin America, highlighting clinical manifestations and regional diagnostic challenges
Background:
FXTAS is a progressive neurodegenerative disorder caused by premutation expansions in the FMR1 gene, often characterized by intention tremor, gait ataxia, parkinsonian features, and cognitive decline. While the prevalence and impact of FXTAS have not been widely studied in Latin America, several case reports and studies offer valuable information on its occurrence and clinical features. Colombia, particularly the town of Ricaurte, Valle del Cauca, has one of the highest reported prevalences of Fragile X Syndrome (FXS) worldwide
Design/Methods:
A scoping review was conducted, including studies from Latin American countries that explicitly reported patients with FXS and a documented FMR1 premutation presenting with FXTAS, or other premutation-associated phenotypes. Eligible studies were screened by two independent reviewers by titles and abstracts using the web-based application Rayyan
Results:
29 studies were included, identifying 35 patients diagnosed with FXTAS, mainly from Brazil, Colombia, Mexico, and Chile. Clinical manifestations included tremor, ataxia, parkinsonism, and cognitive decline. Neuroimaging often showed middle cerebellar peduncle hyperintensities, splenium compromise, and general brain atrophy. Beyond FXTAS, 290 FMR1 premutation carriers without FXTAS were included, presenting with conditions such as premature ovarian failure, psychiatric symptoms and cognitive impairment. Diagnostic confirmation was mainly achieved through PCR and Southern Blot testing.
Conclusions:
FXTAS remains highly underdiagnosed and underreported in Latin America, regardless of clusters with high FMR1 premutation prevalence. The variable penetrance of the premutation produces a heterogeneous and sometimes atypical clinical-radiological spectrum that overlaps with other disorders, complicating the diagnosis. Although molecular and imaging methods are available, more advanced and targeted technologies are needed. Addressing socioeconomic disparities and promoting regional research are essential to improve the diagnosis and treatment of FXTAS and FMR1-related phenotypes in Latin America.
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