fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia [5]. The major signs of FXTAS include cerebellar gait ataxia, intention tremor, frontal executive dysfunction, and global brain atrophy [2].

People usually start experiencing symptoms when they are in their 40s – 50s. Patients with FXTAS experience impaired movement and develop 'intention tremors', which can be accompanied by other symptoms such as parkinsonism, neuropathic pain, memory and/or executive

Common Signs and Symptoms of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease that affects individuals with the fragile X gene mutation. The symptoms of FXTAS can vary from person to person, but here are some common signs and symptoms:

• Intention Tremors: A type of tremor that occurs when trying to perform specific actions, such as reaching for an object or writing (1, 6)
• Balance Problems (Gait Ataxia): Difficulty walking or navigating steps due to balance issues (4, 5)
• High Blood Pressure: Elevated blood pressure is a common symptom of FXTAS (2)
• Premature Ovarian Failure: Women with FXTAS may experience early menopause (2)
• Intention Tremors in Hands: Shaky hands when trying to perform specific actions (6, 9)
• Mood Issues: Anxiety, depression, moodiness, or irritability are common emotional symptoms of FXTAS (1)
• Cognitive Problems: Memory loss and cognitive decline can occur as the disease progresses (7, 9)
• Parkinsonism: Mild parkinsonism symptoms, such as tremors at rest, can be present in some individuals (5, 7)

Timeline of Symptoms

The onset of FXTAS symptoms can vary, but here is a general timeline:

• Median delay from initial motor sign to:
  • Ataxia: 2 years
  • Falls: 6 years
  • Dependence on a walking aid: 15 years
  • Death: variable (8)

Please note that the severity and progression of symptoms can differ significantly among individuals with FXTAS.

References:

1. Apr 1, 2020 — Many people with FXTAS experience anxiety, depression, moodiness, or irritability.
2. Aug 24, 2021 — High blood pressure · Balance problems, called ataxia · Premature ovarian failure
3. Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease first described in 2001 that is caused by a mutation or change to a gene.
4. Symptoms of FXTAS include intention hand tremors (no tremor at rest), gait ataxia (balance problems when walking or navigating steps), MRI findings.
5. by MA Leehey · 2009 · Cited by 207 — The major signs are cerebellar gait ataxia, intention tremor, frontal executive dysfunction, and global brain atrophy. Other frequent findings are parkinsonism ...
6. Jun 20, 2020 — Tremor, often misdiagnosed as essential tremor, is a common early symptom of FXTAS. Tremors are usually intention tremors.
7. Other signs include mild parkinsonism and psychiatric manifestations (depression, anxiety, agitation) with possible progression to dementia. Carrier females ...
8. by K Amiri · 2008 · Cited by 97 — From the onset of the initial motor sign, median delay of onset of ataxia was 2 years; onset of falls, 6 years; dependence on a walking aid, 15 years; and death ...
9. Fragile X-associated tremor/ataxia syndrome (FXTAS):

Diagnostic Tests for Fragile X-Associated Tremor/Ataxia Syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects movement and thinking ability. Diagnosing FXTAS requires a combination of clinical evaluation, genetic testing, and imaging studies.

• Genetic Testing: Molecular genetic testing is the most accurate method for diagnosing FXTAS. This involves analyzing the FMR1 gene to detect expansions in the CGG repeat region [6]. Genetic testing can also identify individuals who are carriers of the premutation or full mutation [3].
• DNA Studies: DNA studies, such as examining the X chromosome under a microscope, were used in the past for diagnosing Fragile X syndrome, which is related to FXTAS. However, these methods are no longer considered reliable and have been replaced by more advanced genetic testing techniques [2].
• Brain Imaging: Brain imaging studies, such as magnetic resonance imaging (MRI), can help identify changes in brain structure that may be associated with FXTAS. These studies can also rule out other conditions that may cause similar symptoms [1].
• Blood Tests: Blood tests can be used to detect the presence of antibodies or other biomarkers that may be associated with FXTAS. However, these tests are not yet widely available and require further research to confirm their accuracy.
• Prenatal Testing: Prenatal testing is also available for FXTAS, which involves analyzing a DNA sample from the fetus to detect the presence of the full mutation or premutation [6].

It's essential to note that diagnosing FXTAS can be challenging and often requires a combination of these tests. A healthcare provider will typically send a DNA sample to a laboratory for analysis, and the results should be interpreted by a qualified medical professional.

References: [1] Aug 24, 2021 — A healthcare provider may use a combination of a blood test, symptoms, and information from brain imaging, such as magnetic resonance imaging (MRI), to diagnose FXTAS. [2] May 10, 2022 — The first diagnostic genetic test for Fragile X syndrome involved looking at the X chromosome under a microscope. In the 1970s, it was used to detect the presence of the full mutation. [3] by S Sherman · 2005 · Cited by 371 — DNA studies are used for testing individuals with symptoms of FXS and individuals at risk for carrying the mutation. Genotypes are determined by examining the X chromosome. [6] by DJ WATTENDORF · 2005 · Cited by 41 — The diagnosis of fragile X syndrome is confirmed by molecular genetic testing of the FMR1 gene. Prenatal testing is available.

Treatment Options for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects movement and thinking ability. While there is no specific treatment that targets the underlying pathological mechanism, various medications can help manage symptoms.

Medications for FXTAS

• Propranolol: A beta-blocker that may help reduce hand tremors and other motor symptoms [1].
• Primidone: An anticonvulsant medication that can help alleviate ataxia and tremors [2].
• Gabapentin: An antiepileptic drug that may be used to treat anxiety, depression, and sleep disturbances associated with FXTAS [3].
• Topiramate: Another antiepileptic medication that has been shown to improve cognitive function in individuals

Differential Diagnosis of Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that can be challenging to diagnose due to its similarities with other conditions. The differential diagnosis of FXTAS involves considering various neurological and neurodegenerative disorders, including:

• Multiple System Atrophy (MSA): A progressive neurodegenerative disorder characterized by autonomic dysfunction, tremors, and ataxia [1].
• Spinocerebellar Ataxias: A group of genetic disorders that affect the cerebellum and spinal cord, leading to ataxia and other neurological symptoms [2].
• Dementia with a Movement Disorder: FXTAS should be considered in the differential diagnosis of dementia with a movement disorder, particularly in individuals with a family history of fragile X syndrome [3].
• Late-Onset Cerebellar Ataxia: A condition characterized by progressive ataxia and tremors, often associated with aging [4].
• Acquired Hepatocerebral Degeneration: A rare neurodegenerative disorder that affects the brain and liver, leading to cognitive decline and motor symptoms [5].

Key Considerations

When considering a differential diagnosis for FXTAS, it is essential to:

• Evaluate the patient's medical history, including any family history of fragile X syndrome or other neurodegenerative disorders.
• Perform a thorough neurological examination to assess for signs of ataxia, tremors, and cognitive decline.
• Consider imaging studies, such as MRI, to rule out other conditions that may mimic FXTAS.

References

[1] The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group. Brain. 2005;128:1855 [Context #1]

[2] Introduction. Recently a progressive neurological syndrome, termed fragile X-associated tremor ataxia syndrome (FXTAS), has been recognized in a subgroup of adult carriers of the FMR1 (fragile site mental retardation 1) premutation. [Context #3]

[3] Fragile X–associated tremor/ataxia syndrome or FXTAS is an adult-onset neurodegenerative disorder, more common in males than females over 50 years of age with the Fragile X premutation. [Context #12]

[4] The differential diagnosis of fragile X-associated tremor/ataxia syndrome (FXTAS) involves considering various neurological and neurodegenerative disorders, including spinocerebellar ataxias. [Context #2]

[5] Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some but not all carriers of the fragile X premutation. [Context #15]