Fragile X Syndrome (FMR1)
Fragile X syndrome is a pan-ethnic disorder caused by expansion of the trinucleotide CGG repeat in the 5 untranslated portion of the FMR1 gene on the X chromosome. It is inherited in an X-linked manner, and therefore affects predominantly males. It is the most common form of inherited intellectual disability. Males with the full repeat expansion (> 200 CGG repeats) exhibit severe intellectual disability, autistic and hyperactive behaviors, seizures, and a characteristic facial appearance. Approximately 50% of females who carry the full repeat expansion will have learning disabilities or mild intellectual disability. Both males and females with a premutation (between 55 and 200 CGG repeats) are at risk of developing Fragile X tremor/ataxia syndrome (FXTAS) in their 50s or 60s. FXTAS is characterized by movement problems similar to those in Parkinsons disease, as well as numbness and development of behavioral and psychiatric issues. Approximately 33% of males with premutations and 5-10% of female premutation carriers will develop FXTAS. Female carriers of a premutation are also at risk of developing premature ovarian failure. Life expectancy is normal for both patients with Fragile X syndrome and may be mildly reduced in patients with FXTAS.
For information about carrier frequency and residual risk, please see the residual risk table.