Fragile X-associated tremor/ataxia syndrome
|Fragile X-associated tremor/ataxia syndrome|
|Classification and external resources|
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder associated with problems with movement, memory, and the autonomic nervous system. Though it also involves the fragile X gene, fragile X syndrome is a much different clinical syndrome. As RNA-binding protein Sam68 was found to control the proper synaptic function in dendrites, loss of Sam68 results in abnormal posttranscriptional regulation and ultimately leads to neurological disorders such as fragile X-associated tremor/ataxia syndrome.
FXTAS can present with many of the same symptoms of multiple system atrophy, and often includes parkinsonism, dysautonomia, peripheral neuropathy, and dementia. It is caused by a trinucleotide repeat disorder in the fragile X mental retardation 1 gene, FMR1. It most often occurs in men, but can present in women. There is no cure for FXTAS, but several of the symptoms can be made better with medication.
The physical symptoms of FXTAS include an intention tremor, ataxia, and parkinsonism (this includes small, shuffling steps, muscle rigidity and slowed speech), as well as neuropathic symptoms. As the disease progresses to the more advanced stages, an individual with FXTAS is also at risk of autonomic dysfunction. This includes hypertension, bowel and bladder dysfunction, and impotence.
An individual with FXTAS may also exhibit the following symptoms: a decrease in cognition, which includes diminishing short-term memory and executive function skills, declining math and spelling abilities and decision-making abilities. FXTAS may also result in changes in personality, due to alterations of the limbic area in the brain. This includes increased irritability, angry outbursts, and impulsive behaviour
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 spanning multiple years or decades. Alternatively, symptoms may progress rapidly.
The medical management of FXTAS aims to reduce the level of disability and minimize symptoms. Presently, there are many gaps in the research on the management of FXTAS, as the disorder was first described in the literature in 2001. There is no treatment modality aimed at reversing the pathogenesis of FXTAS. However, there are a variety of drug therapies that are being utilized in the management of FXTAS symptoms, although there is a lack of randomized control trials assessing the efficacy these therapies and support is limited to anecdotal evidence. Therefore many of the treatments are based on what has been helpful in disorders with similar clinical presentations
- Amiri et al. Fragile X–Associated Tremor/Ataxia Syndrome. Archives of Neurology. VOL 65 (NO. 1), Jan 2008
- Hagerman, PJ; Hagerman RJ (2004). "Fragile X-associated tremor/ataxia syndrome (FXTAS)". Mental Retardation and Developmental Disabilities Research Reviews 10 (1): 25–30.
- Berry-Kravis, E; Abrams, L., Coffey, S.M., Hall, D.A., Greco, C., Gane, L.W., Grigsby, J., Bourgeois, J.A., Finucane, B., Jacquemont, S., Brunberg, J.A., Zhang, L., Lin, J., Tassone, F., Hagerman, P.J., Hagerman, R.J., & Leehey, M.A (2007). "Fragile X-Associated Tremor/Ataxia Syndrome: Clinical Features, Genetics, and Testing Guidelines". Movement Disorders 22 (14): 2018–2030.
- Hagerman, R.J.; Hall, D.A., Coffey, S., Leehey, M., Bourgeois, J., Gould, J., Zhang, L., Seritan, A., Berry-Kravis, E., Olichney, J., Miller, J.W., Fong, A.L., Carpenter, R., Bodine, C., Gane, L.W., Rainin, E., Hagerman, H., & Hagerman, P.J. (2008). "Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems.". Clinical Intervention in Aging 3 (2): 251–262.