Edit concept Question Editor Create issue ticket

Fragile X-Associated Tremor - Ataxia Syndrome

FXTAS Syndrome


Presentation

  • The clinical presentation is heterogeneous, with individuals presenting with varied dominating signs, such as tremor, dementia, or neuropathy.[ncbi.nlm.nih.gov]
  • In this report, we present premutation carrier sisters in whom severity of clinical signs correlated with a molecular pattern of X-inactivation favoring higher expression of the premutation allele.[ncbi.nlm.nih.gov]
  • Here we present a sibpair of two affected brothers presenting with very different symptoms (typical FXTAS versus essential tremor-like), disease progression, and MRI findings, illustrating broad intrafamilial variability of FXTAS.[ncbi.nlm.nih.gov]
  • Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS.[ncbi.nlm.nih.gov]
  • However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS).[ncbi.nlm.nih.gov]
Asymptomatic
  • Asymptomatic carriers performed worse than controls on ECF and declarative learning and memory.[ncbi.nlm.nih.gov]
  • […] vermis and hemisphere in the asymptomatic premutation group.[ncbi.nlm.nih.gov]
  • The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI.[ncbi.nlm.nih.gov]
  • Asymptomatic premutation carriers performed similarly to controls on all but two measures of executive functioning.[ncbi.nlm.nih.gov]
  • METHOD: We issued a call for papers for the special issue, highlighting the primary objective of familiarizing clinical neuropsychologists with FXTAS, and with the neuropsychological phenotype of both male and female asymptomatic carriers.[ncbi.nlm.nih.gov]
Progressive Dementia
  • Abstract This case study describes a 65-year-old man initially diagnosed with an atypical rapidly progressive dementia who subsequently participated in a research project at the MIND Institute at the University of California-Davis, where he was diagnosed[ncbi.nlm.nih.gov]
  • An atypical progressive dementia in a male carrier of the fragile X premutation: an example of fragile X-associated tremor/ataxia syndrome. Applied Neuropsychology, 12 (3), 169–178. PubMed CrossRef Olichney, J. M., Chan, S. H., Wong, L.[springermedizin.de]
Diplopia
  • Abstract We present a case report of an 80-year-old man with Fragile X-associated tremor/ataxia syndrome (FXTAS) and acquired diplopia, strabismus, and other oculomotor abnormalities.[ncbi.nlm.nih.gov]
Suggestibility
  • Previous research suggests that cognitive and psychiatric features of FXTAS may include primary impairments in executive function and increased vulnerability to mood and anxiety disorders.[ncbi.nlm.nih.gov]
  • Finally, the presence of cellular dysregulation in older adults who do not present clinical features of FXTAS may suggest that additional genetic or environmental protective factors may play a role in the pathogenesis of FXTAS.[ncbi.nlm.nih.gov]
  • Since the identification of the first microRNAs (miRNAs) and their role in normal development, several studies have associated them with neurodegenerative diseases such as Parkinson, Alzheimer and Huntington diseases, suggesting that they play a key role[ncbi.nlm.nih.gov]
  • A functional connection between FXTAS and neuropathy has been suggested by the presence of lamin A/C in the intranuclear, neuronal and astrocytic inclusions of FXTAS, since mutations in lamin A/C are known to give rise to an axonal form of CMT. 2007 Wiley-Liss[ncbi.nlm.nih.gov]
  • In these women with a common genetic background, we suggest that symptom severity may be dictated by X-inactivation, and thus a higher percentage of cells producing the premutation-containing mRNA result in increased toxicity and disease.[ncbi.nlm.nih.gov]
Gait Ataxia
  • He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans.[ncbi.nlm.nih.gov]
  • It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings.[ncbi.nlm.nih.gov]
  • Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the[ncbi.nlm.nih.gov]
  • The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia.[ncbi.nlm.nih.gov]
  • Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment.[ncbi.nlm.nih.gov]
Cognitive Deficit
  • Abstract Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established.[ncbi.nlm.nih.gov]
  • The study was designed to define the nature of cognitive deficits affecting male premutation carriers with and without FXTAS.[ncbi.nlm.nih.gov]
  • BACKGROUND: FXTAS, a newly identified phenotype affecting older male carriers of the fragile X premutation allele, is a progressive disorder marked by gait ataxia, action tremor, peripheral neuropathy, executive cognitive deficits, generalized brain atrophy[ncbi.nlm.nih.gov]
  • Individuals with FXTAS have significant cognitive deficits, on the order of those in AD although the cognitive profiles in these dementias are not similar.[ncbi.nlm.nih.gov]
  • Abstract Older FMR1 premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder manifesting cognitive deficits that often subsequently progress to dementia.[ncbi.nlm.nih.gov]
Action Tremor
  • There is no established treatment.The 66-year-old right-handed grandfather of a boy with fragile X syndrome, a carrier of premutation alleles of FMR1 gene, developed an action tremor in his right hand when writing.[ncbi.nlm.nih.gov]
  • Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment.[ncbi.nlm.nih.gov]
  • BACKGROUND: FXTAS, a newly identified phenotype affecting older male carriers of the fragile X premutation allele, is a progressive disorder marked by gait ataxia, action tremor, peripheral neuropathy, executive cognitive deficits, generalized brain atrophy[ncbi.nlm.nih.gov]
  • Symptoms include gait ataxia, action tremor, and cognitive impairment.[ncbi.nlm.nih.gov]
  • Core features of FXTAS include progressive action tremor and gait ataxia; with frequent, more variable features of cognitive decline, especially executive dysfunction, parkinsonism, neuropathy, and autonomic dysfunction.[ncbi.nlm.nih.gov]
Mild Cognitive Impairment
  • Their more severe reduction in N400 repetition effect, than P600, is in contrast to the reverse pattern reported in amnestic mild cognitive impairment and incipient Alzheimer's disease (Olichney et al., 2008).[ncbi.nlm.nih.gov]
  • Over the next few years he developed mild cognitive impairment, gait ataxia and intention tremor. Brain MRI demonstrated the MCP sign and diffuse atrophy.[jnnp.bmj.com]
Postural Instability
  • However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS.[ncbi.nlm.nih.gov]
  • A clinical diagnosis of progressive supranuclear palsy (PSP) was made due to the rapid motor deterioration, postural instability, restriction of downgaze and absence of L-dopa response. He died of pulmonary embolism at age 59.[jnnp.bmj.com]

Treatment

  • These results suggest that memantine treatment may have beneficial effects on verbal memory in FXTAS.[ncbi.nlm.nih.gov]
  • The current review summarizes what is currently known regarding the symptomatic treatment, or potential for treatment, of FXTAS.[ncbi.nlm.nih.gov]
  • This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene.[ncbi.nlm.nih.gov]
  • Treatment is empirical, based on anecdotal experience and on knowledge of what works for symptoms of other disorders that also exist in FXTAS.[ncbi.nlm.nih.gov]
  • Currently, no effective treatment is available.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis The prognosis depends on the speed of progression of the disease, which is highly variable. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • This includes increased irritability, angry outbursts, and impulsive behaviour [2] Prognosis and Medical Management The progression of symptoms varies widely between each case of FXTAS; the onset of symptoms may be gradual, with progression of the disease[ipfs.io]
  • Furthermore, mitochondrial outcomes can identify endophenotypes among carriers and are robust predictors of the premutation diagnosis before the onset of FXTAS, with the potential to be used as markers of prognosis and/or as readouts of pharmacological[ncbi.nlm.nih.gov]
  • Additionally, occupational and physical therapy may help to improve function.. [8] Prognosis [ edit ] The progression of symptoms varies widely between each case of FXTAS; the onset of symptoms may be gradual, with progression of the disease spanning[en.wikipedia.org]
  • Prognosis following cardiac arrest or acute brain injury.[practicalneurology.com]

Etiology

  • The etiology is expansion of a trinucleotide repeat to the premutation range (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene.[ncbi.nlm.nih.gov]
  • Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or 200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures.[ncbi.nlm.nih.gov]
  • Taken together, our data strongly indicate a functional role for 5hmC-mediated epigenetic modulation in the etiology of FXTAS, possibly through the regulation of transcription.[ncbi.nlm.nih.gov]
  • Etiology FXTAS is caused by a CGG trinucleotide repeat expansion (55-200 repeats) in the permutation range of the FMR1 gene (Xq27.3).[orpha.net]
  • The Fragile-X-Premutation: A Maturing Perspective Etiology Its aetiology is still unknown, but molecular investigation in patient affect have led to the identification of a number of candidate genes, the most significant single gene associated with FXTAS[flipper.diff.org]

Epidemiology

  • Summary Epidemiology Prevalence and incidence are unknown. The disease primarily affects males and there is a lifetime cumulated risk for men in the general population of about 1/8,000.[orpha.net]
  • Wikipedia Omim Epidemiology Premutation alleles of the FMR1 gene are relatively common in the general population, carried by 1 in 130-250 females and 1 in 500-800 males.[flipper.diff.org]
  • "Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment". Tremor and Other Hyperkinetic Movements. 2. doi : 10.7916/D8HD7TDS. ISSN 2160-8288. PMC 3570061. PMID 23439567.[en.wikipedia.org]
  • In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica.[kerwa.ucr.ac.cr]
  • Quality Utilising the most up-to-date information from patient registries, clinical trials and epidemiology studies to generate accurate patient population estimates.[gii.co.jp]
Sex distribution
Age distribution

Pathophysiology

  • This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene.[ncbi.nlm.nih.gov]
  • The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS. Copyright 2014 Elsevier Ltd. All rights reserved.[ncbi.nlm.nih.gov]
  • CONCLUSIONS AND RELEVANCE: Distinct pathophysiologic processes may underlie the structural impairment of the motor tracts in FXTAS.[ncbi.nlm.nih.gov]
  • These alterations have implications not only for understanding the pathophysiology of FXTAS, but also for the development of new clinical treatments that may incorporate selective iron chelation. Copyright 2014 Elsevier B.V. All rights reserved.[ncbi.nlm.nih.gov]
  • "Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment". Tremor and Other Hyperkinetic Movements. 2. doi : 10.7916/D8HD7TDS. ISSN 2160-8288. PMC 3570061. PMID 23439567.[en.wikipedia.org]

Prevention

  • This need is underscored by recent neuroimaging findings of changes in the central nervous system that consistently appear well before the onset of clinical symptoms, thus creating an opportunity to delay or prevent the appearance of FXTAS. 2015 New York[ncbi.nlm.nih.gov]
  • Driving expression of FMRpolyG enhanced induction of UPS impairment in cell models, while prevention of RAN translation attenuated UPS impairment in cells and suppressed the genetic interaction with UPS manipulation in Drosophila.[ncbi.nlm.nih.gov]
  • Identification of preclinical signs of motor impairments in FXTAS will potentially establish an early intervention window for providing preventative rehabilitation strategies and disease modifying drugs. To cite this abstract in AMA style: J.[mdsabstracts.org]
  • Despite this, there is currently no effective therapeutics for prevention or treatment of most neurodegenerative conditions.[grantome.com]
  • In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica.[kerwa.ucr.ac.cr]

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!