What are Fragile X-associated disorders?
Fragile X-associated disorders are a group of genetic disorders caused by genetic mutations in the FMR1 (Fragile X Mental Retardation 1) gene, which is responsible for cognitive development and female reproductive functions. There are three fragile X-associated disorders, which include Fragile X syndrome (FXS), Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-Associated Primary Ovarian Insufficiency (FXPOI). Fragile X Syndrome (FXS) Fragile X syndrome is the most common form of inherited intellectual disability. It is caused by a full repeat mutation in the FMR1 gene, resulting in no production of FMRP. Symptoms can vary in severity, from learning deficits to mentally retarded, along with physical and behavioral features that mark the symptoms of FXS. People with the premutation of the FMR1 gene do not develop Fragile X syndrome (FXS), but they have increased risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). Premutation of the FMR1 gene leads to overproduction of abnormal mRNA. This affects the normal functioning of the gene, resulting in partial production of FMRP. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Fragile X-associated tremor/ataxia syndrome is a nervous system disorder characterized by late-onset, gradual problems with movement (ataxia), balance, tremor and memory in older adults. It is caused by premutation of the FMR1 gene, resulting in lower than normal amounts of FMRP. People with FXTAS may develop mild symptoms of physical features and emotional problems observed in fragile X syndrome. Fragile X-Associated Primary Ovarian Insufficiency (FXPOI) Fragile X-associated primary ovarian insufficiency is a gynecological disorder characterized by decreased ovary function in females, leading to infertility, irregular periods, early menopause and elevated levels of FSH (follicle stimulating hormone). There are generally two forms of the disorder, overt POI and occult POI. 1. Overt Primary Ovarian Insufficiency Overt POI is the most serious form, where symptoms involve abnormal menstrual periods, elevated FSH levels before age of 40 and in most cases, infertility. 2. Occult Primary Ovarian Insufficiency Occult POI is a milder form of the condition, where menstrual periods are normal, but have reduced fertility in females. People with FXPOI may also develop mild symptoms of physical features and emotional problems observed in fragile X syndrome, since their FMRP production are lower than normal. References: Fragile X-associated Disorders. National Fragile X Foundation Saul RA, Tarleton JC (1998, Updated 2012 Apr 26). FMR1-Related Disorders. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.