Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers

Hall, Deborah A.; Robertson, Erin; Shelton, Annie L.; Losh, Molly; Milá, Montserrat; Granell, Enric Marco; Gómez‐Anson, Beatriz; Martínez‐Cerdeño, Verónica; Grigsby, Jim; Lozano, Reymundo; Hagerman, Randi J.; María, Lorena Santa; Berry‐Kravis, Elizabeth; O’Keefe, Joan A.

doi:10.1007/s12311-016-0799-4

Cited by 38 publications

(29 citation statements)

References 51 publications

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“…More than half of men with FXTAS have an “MCP sign,” or T2 hyperintensity in the MCPs ( Adams et al, 2007 ). Apartis et al (2012) and Hall et al (2016) also described hyperintensity in the splenium of the corpus callosum. This is the first reported case of a patient with FXTAS who presented to the ED with acutely worsening ataxia and was found to have an acute infarct in medial aspect of the left MCP (as well as a chronic infarct in the lateral aspect of the left MCP).…”

Section: Introductionmentioning

confidence: 94%

Acute Stroke in Middle Cerebellar Peduncle in a Patient With FXTAS

2018

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Background: Fragile-X associated tremor/ataxia syndrome (FXTAS) is commonly associated with T2 hyperintensity in the middle cerebellar peduncles (MCP) on magnetic resonance imaging (MRI). However, ischemic stroke in the MCP in a patient with FXTAS has not previously been described.Case Description: A 61-year-old man with hypertension, sleep apnea, obesity, and FXTAS presented to the emergency department with 2 days of worsening balance and nausea which began 2 days after chiropractic neck manipulation. Examination revealed new nystagmus and worsening dysmetria. Workup revealed an acute infarct in the left MCP, atherosclerotic narrowing of the V4 segment of the left vertebral artery, inadequately controlled hypertension, and a LDL of 127.Conclusion: Isolated MCP infarcts are rare and typically associated with hypoperfusion in the setting of vertebral artery disease and neck manipulation. We suspect that underlying neurodegeneration due to FXTAS with superimposed small vessel disease and neck manipulation may have caused preferential damage to the Purkinje cells in the MCP.

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Section: Introductionmentioning

confidence: 94%

Acute Stroke in Middle Cerebellar Peduncle in a Patient With FXTAS

2018

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“…Several deletions and point mutations leading to the production of non-functional proteins have also been described (Okray et al, 2015 and references therein). Individuals with 55–200 CGG repetitions (premutation) do not present FXS symptoms, but may develop two other disorders: Fragile-X Primary Ovarian Insufficiency (FXPOI) (reviewed in Sherman et al, 2014 ) or Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) (reviewed in Hall et al, 2016 ; Dahlhaus, 2018 ). FXTAS has been modeled in Drosophila by overexpressing 90 rCGG repeats alone fused to GFP, which causes a neuron-specific degeneration and the formation of inclusions (Jin et al, 2003 ; Qurashi et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Modeling Fragile X Syndrome in Drosophila

Drozd

Bardoni

Capovilla

2018

Front. Mol. Neurosci.

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Intellectual disability (ID) and autism are hallmarks of Fragile X Syndrome (FXS), a hereditary neurodevelopmental disorder. The gene responsible for FXS is Fragile X Mental Retardation gene 1 (FMR1) encoding the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA metabolism and modulating the expression level of many targets. Most cases of FXS are caused by silencing of FMR1 due to CGG expansions in the 5′-UTR of the gene. Humans also carry the FXR1 and FXR2 paralogs of FMR1 while flies have only one FMR1 gene, here called dFMR1, sharing the same level of sequence homology with all three human genes, but functionally most similar to FMR1. This enables a much easier approach for FMR1 genetic studies. Drosophila has been widely used to investigate FMR1 functions at genetic, cellular, and molecular levels since dFMR1 mutants have many phenotypes in common with the wide spectrum of FMR1 functions that underlay the disease. In this review, we present very recent Drosophila studies investigating FMRP functions at genetic, cellular, molecular, and electrophysiological levels in addition to research on pharmacological treatments in the fly model. These studies have the potential to aid the discovery of pharmacological therapies for FXS.

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“…The MCP sign represents the major radiological diagnostic criterion for FXTAS and confirms a definite diagnosis of FXTAS when it occurs with tremor and/or ataxia ( 8 ). Additional MRI findings include white matter hyperintensities in the periventricular regions and splenium of the corpus callosum (CC) ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Presence of Middle Cerebellar Peduncle Sign in FMR1 Premutation Carriers Without Tremor and Ataxia

et al. 2018

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Here we report five cases of male FMR1 premutation carriers who present without clinical symptoms of the fragile X-associated tremor/ataxia syndrome (FXTAS), but who on MRI demonstrate white matter hyperintensities in the middle cerebellar peduncles (MCP sign) and other brain regions, a rare finding. MCP sign is the major radiological feature of FXTAS; it is therefore remarkable to identify five cases in which this MRI finding is present in the absence of tremor and ataxia, the major clinical features of FXTAS. Subjects underwent a detailed neurological evaluation, neuropsychological testing, molecular testing, and MRI evaluation utilizing T2 imaging described here. Additional white matter disease was present in the corpus callosum in four of the five cases. However, all cases were asymptomatic for motor signs of FXTAS.

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Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers

Cited by 38 publications

References 51 publications

Acute Stroke in Middle Cerebellar Peduncle in a Patient With FXTAS

Acute Stroke in Middle Cerebellar Peduncle in a Patient With FXTAS

Modeling Fragile X Syndrome in Drosophila

Presence of Middle Cerebellar Peduncle Sign in FMR1 Premutation Carriers Without Tremor and Ataxia

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