Fragile X clinical features and neurobiology

The fragile X family of disorders includes those with a full mutation [>200 cytosine-guanine-guanine (CGG) repeats] on the front end of the FMR1 gene who have fragile X syndrome characterized by intellectual disability and behavior problems, including anxiety, social deficits, hyperactivity, hyperarousal, and sometimes aggressive behavior. Also in this family are those with the premutation (55-200 CGG repeats) and they can suffer from the fragile X-associated primary ovarian insufficiency in approximately 20% of women, the fragile X-associated tremor/ataxia syndrome seen in 40% of males and 16% of females who are older than 50 years, and the fragile X-associated neuropsychiatric disorders (FXAND) occurring in approximately 50% of carriers and can include depression, anxiety, chronic fatigue, insomnia, and obsessive-compulsive behavior. The neurobiology associated with these disorders is reviewed in addition to the use of targeted treatments that have the potential to reverse neurobiological abnormalities.