[Fragile X associated tremor/ataxia syndrome: its clinical presentation, pathology, and treatment]

Rev Neurol. 2019 Mar 1;68(5):199-206. doi: 10.33588/rn.6805.2018457.
[Article in Spanish]

Abstract

The fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease associated with the repetition of CGG triplets (55-200 CGG repetitions) in the FMR1 gene. The premutation of the FMR1 gene, contrasting with the full mutation (more than 200 CGG repetitions), presents an increased production of messenger and a similar or slightly decreased production of FMRP protein. FXTAS affects 40% of men and 16% of women carriers of the premutation. It presents with a wide constellation of neurological signs such as intention tremor, cerebellar ataxia, parkinsonism, executive function deficits, peripheral neuropathy and cognitive decline leading to dementia among others. In this review, we present what is currently known about the molecular mechanism, the radiological findings and the pathology, as well as the complexity of the diagnosis and management of FXTAS.

Title: Sindrome de temblor y ataxia asociado al X fragil: presentacion clinica, patologia y tratamiento.

El sindrome de temblor y ataxia asociado al X fragil (FXTAS) es una enfermedad neurodegenerativa relacionada con la premutacion del gen FMR1. Los alelos con premutacion (55-200 repeticiones de CGG), al contrario de los alelos con mutacion completa (mas de 200 repeticiones CGG), tienen una produccion excesiva de ARN mensajero y unos niveles normales o reducidos de proteina. El FXTAS afecta al 40% de los hombres y al 16% de las mujeres portadores de la premutacion de FMR1. Se presenta con una amplia variedad de signos neurologicos, como temblor de intencion, ataxia cerebelosa, parkinsonismo, deficit en la funcion ejecutiva, neuropatia periferica y deterioro cognitivo que conduce a la demencia, entre otros. En esta revision se presenta lo que hasta ahora se conoce del mecanismo molecular, los hallazgos radiologicos y la patologia, asi como tambien la complejidad del diagnostico y el tratamiento del FXTAS.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Ataxia* / diagnosis
  • Ataxia* / diagnostic imaging
  • Ataxia* / genetics
  • Ataxia* / therapy
  • Brain / diagnostic imaging
  • Brain / pathology
  • Deep Brain Stimulation
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome* / diagnosis
  • Fragile X Syndrome* / diagnostic imaging
  • Fragile X Syndrome* / genetics
  • Fragile X Syndrome* / therapy
  • Humans
  • Male
  • Memantine / therapeutic use
  • Neurologic Examination
  • Pregnanolone / therapeutic use
  • Symptom Assessment
  • Tremor* / diagnosis
  • Tremor* / diagnostic imaging
  • Tremor* / etiology
  • Tremor* / genetics
  • Tremor* / therapy

Substances

  • Antidepressive Agents
  • FMR1 protein, human
  • Fragile X Mental Retardation Protein
  • Pregnanolone
  • Memantine

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome