Fragile X-associated tremor/ataxia syndrome-features, mechanisms and management

Research output: Contribution to journalReview article

56 Citations (Scopus)

Abstract

Many physicians are unaware of the many phenotypes associated with the fragile X premutation, an expansion in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats. The most severe of these phenotypes is fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in the majority of ageing male premutation carriers but in fewer than 20% of ageing women with the premutation. The prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, so physicians are likely to see people affected by FXTAS. Fragile X DNA testing is broadly available in the Western world. The clinical phenotype of FXTAS at presentation can vary and includes intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonian features, and psychological disorders, such as depression, anxiety and/or apathy. FXTAS causes brain atrophy and white matter disease, usually in the middle cerebellar peduncles, the periventricular area, and the splenium and/or genu of the corpus callosum. Here, we review the complexities involved in the clinical management of FXTAS and consider how targeted treatment for these clinical features of FXTAS will result from advances in our understanding of the molecular mechanisms that underlie this neurodegenerative disorder. Such targeted approaches should also be more broadly applicable to earlier forms of clinical involvement among premutation carriers.

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalNature Reviews Neurology
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Phenotype
Physicians
Leukoencephalopathies
Apathy
Cerebellar Ataxia
Western World
Corpus Callosum
5' Untranslated Regions
Executive Function
Neuralgia
Tremor
Intellectual Disability
Neurodegenerative Diseases
Atrophy
Fragile X Tremor Ataxia Syndrome
Anxiety
Depression
Psychology
DNA
Brain

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Fragile X-associated tremor/ataxia syndrome-features, mechanisms and management. / Hagerman, Randi J; Hagerman, Paul J.

In: Nature Reviews Neurology, Vol. 12, No. 7, 01.07.2016, p. 403-412.

Research output: Contribution to journalReview article

@article{ebf1ba3f64cc44f2a2057e70e19a7422,
title = "Fragile X-associated tremor/ataxia syndrome-features, mechanisms and management",
abstract = "Many physicians are unaware of the many phenotypes associated with the fragile X premutation, an expansion in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats. The most severe of these phenotypes is fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in the majority of ageing male premutation carriers but in fewer than 20{\%} of ageing women with the premutation. The prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, so physicians are likely to see people affected by FXTAS. Fragile X DNA testing is broadly available in the Western world. The clinical phenotype of FXTAS at presentation can vary and includes intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonian features, and psychological disorders, such as depression, anxiety and/or apathy. FXTAS causes brain atrophy and white matter disease, usually in the middle cerebellar peduncles, the periventricular area, and the splenium and/or genu of the corpus callosum. Here, we review the complexities involved in the clinical management of FXTAS and consider how targeted treatment for these clinical features of FXTAS will result from advances in our understanding of the molecular mechanisms that underlie this neurodegenerative disorder. Such targeted approaches should also be more broadly applicable to earlier forms of clinical involvement among premutation carriers.",
author = "Hagerman, {Randi J} and Hagerman, {Paul J}",
year = "2016",
month = "7",
day = "1",
doi = "10.1038/nrneurol.2016.82",
language = "English (US)",
volume = "12",
pages = "403--412",
journal = "Nature Reviews Neurology",
issn = "1759-4758",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Fragile X-associated tremor/ataxia syndrome-features, mechanisms and management

AU - Hagerman, Randi J

AU - Hagerman, Paul J

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Many physicians are unaware of the many phenotypes associated with the fragile X premutation, an expansion in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats. The most severe of these phenotypes is fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in the majority of ageing male premutation carriers but in fewer than 20% of ageing women with the premutation. The prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, so physicians are likely to see people affected by FXTAS. Fragile X DNA testing is broadly available in the Western world. The clinical phenotype of FXTAS at presentation can vary and includes intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonian features, and psychological disorders, such as depression, anxiety and/or apathy. FXTAS causes brain atrophy and white matter disease, usually in the middle cerebellar peduncles, the periventricular area, and the splenium and/or genu of the corpus callosum. Here, we review the complexities involved in the clinical management of FXTAS and consider how targeted treatment for these clinical features of FXTAS will result from advances in our understanding of the molecular mechanisms that underlie this neurodegenerative disorder. Such targeted approaches should also be more broadly applicable to earlier forms of clinical involvement among premutation carriers.

AB - Many physicians are unaware of the many phenotypes associated with the fragile X premutation, an expansion in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats. The most severe of these phenotypes is fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in the majority of ageing male premutation carriers but in fewer than 20% of ageing women with the premutation. The prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, so physicians are likely to see people affected by FXTAS. Fragile X DNA testing is broadly available in the Western world. The clinical phenotype of FXTAS at presentation can vary and includes intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonian features, and psychological disorders, such as depression, anxiety and/or apathy. FXTAS causes brain atrophy and white matter disease, usually in the middle cerebellar peduncles, the periventricular area, and the splenium and/or genu of the corpus callosum. Here, we review the complexities involved in the clinical management of FXTAS and consider how targeted treatment for these clinical features of FXTAS will result from advances in our understanding of the molecular mechanisms that underlie this neurodegenerative disorder. Such targeted approaches should also be more broadly applicable to earlier forms of clinical involvement among premutation carriers.

UR - http://www.scopus.com/inward/record.url?scp=84976310047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976310047&partnerID=8YFLogxK

U2 - 10.1038/nrneurol.2016.82

DO - 10.1038/nrneurol.2016.82

M3 - Review article

C2 - 27340021

AN - SCOPUS:84976310047

VL - 12

SP - 403

EP - 412

JO - Nature Reviews Neurology

JF - Nature Reviews Neurology

SN - 1759-4758

IS - 7

ER -