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

Hagerman, Randi J.; Hagerman, Paul J.

doi:10.1038/nrneurol.2016.82

Cited by 236 publications

(289 citation statements)

References 160 publications

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“…FMR1 PM, although not responsible for FXS, predisposes ~40%–45% of the male [30,31] and ~8%–16% of the female carriers [31,32] to FXTAS, a condition that is characterized by intention tremor, cerebellar gait ataxia, peripheral neuropathy, parkinsonism, memory/cognitive function deficits and other psychological issues [33,34]. Age-dependent penetrance of FXTAS has been noted in both male and female PM carriers [31], with higher risks reported among individuals aged 70–79 years [31] and ≥80 years [30].…”

Section: Molecular Determinants Of Fxtasmentioning

confidence: 99%

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Rajan‐Babu

Chong

2016

Genes

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Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and autism. Molecular diagnostic testing of FXS and related disorders (fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS)) relies on a combination of polymerase chain reaction (PCR) and Southern blot (SB) for the fragile X mental retardation 1 (FMR1) CGG-repeat expansion and methylation analyses. Recent advancements in PCR-based technologies have enabled the characterization of the complete spectrum of CGG-repeat mutation, with or without methylation assessment, and, as a result, have reduced our reliance on the labor- and time-intensive SB, which is the gold standard FXS diagnostic test. The newer and more robust triplet-primed PCR or TP-PCR assays allow the mapping of AGG interruptions and enable the predictive analysis of the risks of unstable CGG expansion during mother-to-child transmission. In this review, we have summarized the correlation between several molecular elements, including CGG-repeat size, methylation, mosaicism and skewed X-chromosome inactivation, and the extent of clinical involvement in patients with FMR1-related disorders, and reviewed key developments in PCR-based methodologies for the molecular diagnosis of FXS, FXTAS and FXPOI, and large-scale (CGG)n expansion screening in newborns, women of reproductive age and high-risk populations.

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Section: Molecular Determinants Of Fxtasmentioning

confidence: 99%

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Rajan‐Babu

Chong

2016

Genes

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“…In individuals with fragile X-associated tremor/ataxia syndrome, intranuclear inclusions form in both the central nervous system and peripheral tissues (3). Neurons and astrocytes in the cerebellum, basal ganglia, hippocampus and frontal cortex are particularly affected (4).…”

Section: Pathogenesis and Inheritancementioning

confidence: 99%

“…Some patients have experienced a reduction in tremor with the use of beta-blockers and levetiracetam (3). Levodopa can produce improvements in parkinsonian symptoms, and should be tried in patients who experience these (3).…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

Fragilt X-assosiert tremor-ataksi-syndrom

Hoem¹,

Koht²

2017

Tidsskriftet

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“…With these findings, the onset of symptoms can be predicted or a baseline parameter can be anticipated (31).…”

Section: Discussionmentioning

confidence: 99%

Fragile X Syndrome in a Colombian Family

Saldarriaga¹,

Hagerman

Salcedo-Arellano³

et al. 2018

iatreia

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SUMMARYA study was performed on a family from Cali, Colombia in which nine patients were evaluated, three of which presented with intellectual disability with no previous etiological diagnosis.The proband was diagnosed with Fragile X syndrome by DNA molecular testing and, cascade testing, performed on all available family members, identifying two additional individuals with the full mutation and four carriers of a premutation allele.With this report we seek to contribute to Colombian epidemiology of the syndrome and emphasize the importance of diagnosis to provide a comprehensive and specific treatment to those affected. Further we seek to identify premutation carriers in their families or women with a full mutation without the classic phenotype for genetic counseling and education about potential associated pathologies. KEY WORDSFMRP; Fragile X Syndrome; Genetic Counseling; Intellectual Disability IATREIA Vol 31(1) enero-marzo 2018 77 RESUMEN Sindrome X frágil en una Familia ColombianaSe realizó un estudio descriptivo a una familia de Cali, Colombia, en el cual se evaluaron nueve pacientes, tres de los cuales presentaban discapacidad intelectual sin diagnóstico etiológico anterior. El caso índice fue diagnosticado con el síndrome X frágil mediante pruebas moleculares de ADN. Se realizaron pruebas en cascada a todos los miembros de la familia disponibles, identificando dos individuos adicionales con la mutación completa y cuatro portadores del alelo con pre mutación. Con este informe pretendemos contribuir a la epidemiología colombiana del síndrome y destacamos la importancia del diagnóstico etiológico de la discapacidad intelectual y proporcionar un tratamiento integral y específico a las personas afectadas. Además se busca identificar a los portadores de la pre mutación o mujeres con mutación completa sin fenotipo clásico para el asesoramiento genético y la educación sobre posibles patologías asociadas.

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

Cited by 236 publications

References 160 publications

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Fragilt X-assosiert tremor-ataksi-syndrom

Fragile X Syndrome in a Colombian Family

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