Fragile X Tremor/Ataxia Syndrome (FXTAS)
This gene is carried on the X chromosome. Men carry only one copy of the X chromosome, while women carry two. Thus, men with one mutated gene are more likely to be affected. Penetrance is approximately 20%.
Molecular genetics and pathogenesis
FXTAS is due to a moderately expanded repeat in the FMR1 gene, responsible for fragile X mental retardation syndrome in boys. The full mutation, which causes fragile X syndrome, includes over 200 CGG repeats. The "premutation" responsible for FXTAS is 50-200 repeats. Expansion of the premutation to the full mutation occurs when the gene is passed from mother to child.
FXTAS premutations are common in males (typically grandfather), relatives of boys with fragile X syndrome. Rare in females
Onset is usually after age 50. Patients present with progressive ataxia, intention tremor and/or cognitive/behavioral deficits. Anxiety may be present.
Misdiagnosis is common, and includes multiple system atrophy (cerebellar form), essential tremor, and Parkinson's disease.
Symptomatic treatments for tremor, anxiety, and other symptoms may be helpful. A recent double-blind pilot trial in a small number of patients with various forms of ataxia (including FXTAS) indicated that riluzole may offer some benefit for ataxia symptoms (see E-MOVE Article: Riluzole for Cerebellar Ataxia).
Willemsen R, Mientjes E, Oostra BA. FXTAS: a progressive neurologic syndrome associated with Fragile X premutation. Curr Neurol Neurosci Rep. 2005 Sep;5(5):405-410.
PMID: 16131424 Ataxia due to vitamin E deficiency (inherited)