Summary about Disease
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset, progressive neurodegenerative disorder that primarily affects older adult males who are carriers of a premutation in the FMR1 gene. The FMR1 gene is responsible for producing the FMRP protein, which is crucial for brain development. In FXTAS, the expanded CGG repeat in the FMR1 gene (premutation, not full mutation like in Fragile X syndrome) leads to the production of toxic messenger RNA (mRNA) which accumulates in the brain and other tissues, causing cellular damage and dysfunction.
Symptoms
Symptoms of FXTAS typically include:
Tremor: Intention tremor (tremor that occurs during purposeful movement) is common.
Ataxia: Problems with balance and coordination.
Parkinsonism: Symptoms similar to Parkinson's disease, such as rigidity, slow movement (bradykinesia), and postural instability.
Cognitive Decline: Problems with memory, executive function (planning, problem-solving), and attention.
Neuropathy: Peripheral neuropathy, causing numbness, tingling, and pain in the hands and feet.
Autonomic Dysfunction: Problems with blood pressure regulation, bladder control, and bowel function.
Psychiatric Symptoms: Depression, anxiety, irritability, and personality changes.
White Matter Lesions: Visible on brain MRI.
Causes
FXTAS is caused by a premutation in the FMR1 gene on the X chromosome. This premutation involves an expansion of CGG trinucleotide repeats, ranging from 55 to 200 repeats (normal individuals have less than 45 repeats). While individuals with the full mutation (>200 CGG repeats) typically develop Fragile X syndrome (a developmental disability), those with the premutation are at risk for developing FXTAS later in life. The expanded CGG repeat in the premutation leads to the increased production of FMR1 mRNA, which accumulates and becomes toxic to cells, especially in the brain and nervous system.
Medicine Used
There is no specific cure for FXTAS, and treatment focuses on managing the symptoms. Medications used may include:
Tremor: Beta-blockers (e.g., propranolol), primidone, or other anti-tremor medications.
Parkinsonism: Levodopa or other medications used to treat Parkinson's disease.
Cognitive Decline: Medications for memory and cognitive enhancement (e.g., cholinesterase inhibitors) may be considered, although their efficacy in FXTAS is not well-established.
Neuropathy: Medications for neuropathic pain (e.g., gabapentin, pregabalin, duloxetine).
Psychiatric Symptoms: Antidepressants (e.g., SSRIs), anti-anxiety medications, or antipsychotics as needed. Physical therapy, occupational therapy, and speech therapy are also important for managing motor and functional impairments.
Is Communicable
FXTAS is not communicable. It is a genetic disorder caused by a premutation in the FMR1 gene and is not infectious.
Precautions
There are no specific precautions to prevent the spread of FXTAS because it is not contagious. However, individuals who are known carriers of the FMR1 premutation should be aware of the risk of developing FXTAS and the possibility of passing the premutation to their children. Genetic counseling is recommended for individuals with a family history of Fragile X syndrome or FXTAS. Regular neurological evaluations can help monitor for the early signs of FXTAS in at-risk individuals.
How long does an outbreak last?
FXTAS is not an "outbreak" situation, it is a chronic, progressive condition. Symptoms typically develop gradually over several years. The duration of the condition and the rate of progression vary significantly from person to person. There is no defined end date for FXTAS.
How is it diagnosed?
Diagnosis of FXTAS typically involves:
Clinical Evaluation: A thorough neurological examination to assess symptoms such as tremor, ataxia, cognitive decline, and neuropathy.
Brain MRI: To look for characteristic white matter lesions in the brain, particularly in the middle cerebellar peduncles.
Genetic Testing: A blood test to determine the number of CGG repeats in the FMR1 gene. A premutation (55-200 CGG repeats) confirms the genetic basis of FXTAS.
Neuropathology: In some cases, a brain biopsy (usually post-mortem) may be performed to examine brain tissue for characteristic findings of FXTAS, such as the presence of intranuclear inclusions in neurons and astrocytes.
Timeline of Symptoms
The timeline of FXTAS symptoms varies but typically follows this pattern:
Onset: Usually after age 50, often in the 60s or 70s.
Early Symptoms: Subtle changes in balance, tremor (often starting in the hands), mild cognitive difficulties.
Progression: Over years, the tremor becomes more pronounced, ataxia worsens, cognitive decline becomes more apparent, and other symptoms such as neuropathy, autonomic dysfunction, and psychiatric symptoms may emerge.
Late Stages: Significant motor impairment, cognitive impairment, and dependence on assistance for daily activities. The rate of progression varies considerably among individuals.
Important Considerations
Genetic Counseling: Individuals with a family history of Fragile X syndrome or FXTAS should consider genetic counseling to understand their risk and the risk to their offspring.
Early Diagnosis: Early diagnosis and intervention can help manage symptoms and improve quality of life.
Multidisciplinary Care: Management of FXTAS requires a multidisciplinary approach involving neurologists, psychiatrists, physical therapists, occupational therapists, and other specialists.
Support Groups: Joining support groups can provide valuable emotional support and information for individuals with FXTAS and their families.
Research: Ongoing research is aimed at better understanding the mechanisms of FXTAS and developing effective treatments.
Women: While FXTAS primarily affects men, women with the premutation can also develop milder symptoms. They can also pass the premutation onto their children.