Fragile X Disorders

Fragile X Premutation

Background and Prevalence

The Fragile X premutation may also present with a spectrum of disorders related to the fragile X gene, FMR1. Estimated frequencies of individuals carrying the premutation are approximately 1:850 males and 1:300 females.

Cause

Similar to fragile X syndrome, the fragile X premutation results from a mutation in the FMR1 gene, in which 55-200 CGG repeats are present. Individuals who have the premutation are commonly referred to as premutation “carriers.” Female premutation carriers are at risk of having the number of CGG repeats expand when passing on the gene mutation to a child. 

Symptoms

There are three well-characterized conditions, Fragile X Tremor Ataxia Syndrome (FXTAS), Fragile X Premature Ovarian Insufficiency (FXPOI), and most recently, Fragile X-Associated Neuropsychiatric Disorders (FXAND) that have been associated with the premutation, in addition to a wide spectrum of other medical, reproductive, cognitive, and psychiatric features, primarily in females, suggested to be associated with premutation in the FMR1 gene. Cognitive abilities are often within the normal range and may be associated with learning disabilities and/or executive functioning problems.  Psychological problems, such as anxiety and depression, are relatively common among individuals with the premutation.

Treatment

As with fragile X syndrome, there is no cure for the fragile X premutation. Given that symptoms of the premutation are highly variable and can change of time, we recommend adult patients with the premutation be evaluated in our premutation carrier clinic at the University Hospital to determine if further evaluation of cognitive, behavioral, or psychological problems associated with the premutation would be helpful and direct treatments, when available. Several web sites, including the National Fragile X Foundation (fragilex.org) provide information about disorders related to mutations of the FMR1 gene.