Slower Manual Movement Seen in Fragile X Premutation Carriers Before Disease Onset
Carriers of the fragile X premutation who have not yet developed the disease have slower motor movements associated with mutation length and increased age.
The study, “Age- and CGG Repeat-Related Slowing of Manual Movement in Fragile X Carriers: A Prodrome of Fragile X-Associated Tremor Ataxia Syndrome?” was published in the journal Movement Disorders.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disease that affects many patients that carry the fragile X premutation.
A premutation carrier is an individual that has from 55 and 200 CGG repeats in the fragile X gene FMR1. The full mutation is defined as over 200 CGG repeats, and results in fragile X syndrome.
Patients with FXTAS demonstrate progressive gait ataxia, low-frequency tremor, parkinsonism, dementia, impaired organ function, and damage to the nerves. However, this disease only shows up in some patients with the premutation, with one study suggesting that 47% of men with the premutation will develop FXTAS by the eighth decade of their life.
Currently, little is known about prediction of onset, rate of progression, and treatment of this neurodegenerative disease. So researchers set out to conduct a long-term study of premutation carriers and recently presented the results from the baseline assessments of this ongoing research.
The study group consists of 73 men, of which 48 have the fragile X mental retardation 1 (FMR1) premutation, with 25 age-matched control patients from ages 40-75.
At the time of enrollment, none of the patients met the criteria required for a diagnosis of FXTAS or had any clinically significant tremor or ataxia, as determined by a blinded neurological examination.
Traits evaluated include visual memory, spatial working memory, response inhibition, motor speed and control, planning and problem solving, sustained attention, and a standardized movement disorder.
Results showed that, contrary to what was expected, there were no significant differences between premutation carriers and controls on any measure of executive function, including response inhibition, sustained visual attention, problem solving, and visual spatial memory.
However, patients with the premutation had significantly longer manual movement and reaction times than controls. After additional exams, researchers found a significant link between slower movement times and older carriers with higher CGG repeat alleles.
These results indicate that the longer the CGG repeat and the older the patient, the slower they move. One question, however, is why motor slowing occurs before any neurological symptom.
Researchers believe that early-developing alterations in specific brain regions, previously shown in MRI studies, may be the reason why motor slowing occurs before any clinically observable neurological symptoms in patients with FXTAS.