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Las expansiones GAA-FGF14 y las variantes CACNA1A: superposición fenotípica e implicaciones diagnósticas

Elisabetta Indelicato¹, Zofia Fleszar^2,3, David Pellerin^4,5

¹Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Movement disorders : official journal of the Movement Disorder Society

|August 29, 2025

Resumen

La ataxia espinocerebelosa 27B (SCA27B) es causada por expansiones repetidas del FGF14. Este estudio encontró SCA27B en el 9% de los pacientes con variantes CACNA1A, lo que sugiere la reevaluación de la ataxia de aparición tardía.

Área de la Ciencia:

Neurogenética
Neurología
La genómica

Sus antecedentes:

La ataxia espinocerebelosa 27B (SCA27B) está relacionada con las expansiones repetidas intrónicas del FGF14.
SCA27B presenta ataxia cerebelosa crónica y síntomas episódicos, que se superponen con trastornos del espectro CACNA1A.

Objetivo del estudio:

Determinar la frecuencia de las expansiones repetidas de GAA-FGF14 en pacientes inicialmente diagnosticados con ataxia relacionada con CACNA1A.
Investigar la utilidad diagnóstica de las pruebas de FGF14 en esta cohorte de pacientes.

Principales métodos:

Diseño de estudio transversal y multicéntrico.
Pruebas genéticas para expansiones repetidas de GAA-FGF14 en pacientes con variantes de CACNA1A.
Reclasificación de las variantes de CACNA1A de importancia incierta (VUS).

Principales resultados:

Se identificaron expansiones patógenas de GAA-FGF14 (≥250 repeticiones) en el 9% (6/67) de los pacientes con variantes de CACNA1A.
Los pacientes con expansiones de GAA-FGF14 presentaron una aparición tardía (> 40 años) y portaban CACNA1A VUS.
Cuatro de los seis pacientes con expansiones de GAA-FGF14 tuvieron sus CACNA1A VUS reclasificados como probablemente benignos, confirmando el diagnóstico de SCA27B.

Conclusiones:

La ataxia de inicio tardío atribuida inicialmente a las variantes CACNA1A justifica una reevaluación para SCA27B.
Las pruebas genéticas para las expansiones repetidas de GAA-FGF14 son cruciales, especialmente cuando están presentes variantes de CACNA1A de importancia incierta.

Palabras clave:

CACNA1A y CACNA2A Ataxia por GAA y FGF14 SCA27B (en inglés)Ataxia episódica Ataxia espinocerebelosa 27B

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