Fragile X syndrome

Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder.^[1] The average IQ in males with FXS is under 55, while affected females tend to be in the borderline to normal range, typically around 70–85.^[3][4] Physical features may include a long and narrow face, large ears, flexible fingers, and large testicles.^[1] About a third of those affected have features of autism such as problems with social interactions and delayed speech.^[1] Hyperactivity is common, and seizures occur in about 10%.^[1] Males are usually more affected than females.^[1]

This disorder and finding of fragile X syndrome has an X-linked dominant inheritance.^[5] It is typically caused by an expansion of the CGG triplet repeat within the FMR1 (fragile X messenger ribonucleoprotein 1) gene on the X chromosome.^[1] This results in silencing (methylation) of this part of the gene and a deficiency of the resultant protein (FMRP), which is required for the normal development of connections between neurons.^[1] Diagnosis requires genetic testing to determine the number of CGG repeats in the FMR1 gene.^[6] Normally, there are between 5 and 40 repeats; fragile X syndrome occurs with more than 200.^[1] A premutation is said to be present when the gene has between 55 and 200 repeats; females with a premutation have an increased risk of having an affected child.^[1] Testing for premutation carriers may allow for genetic counseling.^[6]

There is no cure.^[2] Early intervention is recommended, as it provides the most opportunity for developing a full range of skills.^[7] These interventions may include special education, occupational therapy, speech therapy, physical therapy, or behavioral therapy.^[2][8] Medications may be used to treat associated seizures, mood problems, aggressive behavior, or ADHD.^[9] Fragile X syndrome tends to show more symptoms on affected males since females have another X chromosome which can compensate for the damaged one.^[4][10]