The professionals and parents who are part of the Fragile X Clinical and Research Consortium (FXCRC) have updated treatment and intervention recommendations for fragile X-associated tremor/ataxia syndrome (FXTAS).
FXTAS is a late-onset neurodegenerative disease that was first identified in older, mainly male, grandparents and parents of individuals with fragile X syndrome (FXS).
It is caused by 55 to 200 CGG repeats in the fragile X gene FMR1, whereas the full mutation is defined as over 200 CGG repeats and results in fragile X syndrome. Among people who carry this so-called pre-mutation, about 40 percent of men older than 50 and 8-16 percent of women older than 40 develop FXTAS.
FXTAS leads to progressive, uncoordinated walking, low-frequency tremors, Parkinsonism, dementia, impaired organ function, and nerve damage.
There is still a lot to learn about the prediction of disease onset, rate of progression, and treatment of this neurodegenerative disease, but increasing efforts are being made to improve patients’ care and quality of life.
The Fragile X Clinical and Research Consortium was created in 2006 by the National Fragile X Foundation (NFXF) in response to the growing needs of families whose members have a fragile X-associated disorder. Since then, 29 clinics staffed by specialists experienced in the evaluation and treatment of all FSX conditions have been established.
The FXCRC and the NFXF joined forces with the Centers for Disease Control to develop the largest database of fragile X patients in the U.S., called FORWARD – the Fragile X Online Registry With Accessible Research Database.
FORWARD contains data from both individuals with FXS and their family members, and its mission is to improve the care and quality of life for those living with these syndromes.
FXCRC’s experts and parents have been developing treatment and intervention recommendations based on information collected in the FORWARD database, along with other scientific research.
The recommendations cover the three primary fragile X-associated disorders — fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency — and are available at the NFXF’s website in the form of 18 documents.
The documents address several FXS subjects, such as genetic counseling and family support, assessment of the disease, medication, complementary and alternative therapies, educational guidelines, behavioral problems, sleep disturbances, toileting issues, hyperarousal (a state of excessive physical and mental tension), seizures, and autism spectrum disorder.
The recently updated document concerns FXTAS and explores its diagnosis and current treatment guidelines.
While the goal of FXTAS therapy is to reduce symptoms and slow disease progression, so far no medication has been shown to effectively prevent disease progression in controlled clinical trials. Thus, current FXTAS treatment is limited to symptom reduction.
Treatment recommendations have been based on the experience of case reports or on the knowledge of similar diseases, and the FXTAS document indicates some of the therapies that may be considered for the treatment of FXTAS, including medications used for essential tremors and Parkinson’s disease; deep brain stimulator surgery for tremors; amantadine, buspirone, varenicline, riluzole, or Ampyra for cerebellar dysfunction (although none have proven efficacy in FXTAS); or serotonin inhibitors to treat psychiatric symptoms.
It is also noted that FXTAS treatment should be personalized for each patient, as symptoms vary between individuals, and should use global approaches including medication, rehabilitative interventions, and psychological counseling.