Fragile X syndrome

Fragile X syndrome
Other names	Martin–Bell syndrome,[1] Escalante syndrome
Boy with protruding ears characteristic of fragile X syndrome
Specialty	Medical genetics, pediatrics, psychiatry
Symptoms	Intellectual disability, long and narrow face, large ears, flexible fingers, large testicles[1]
Complications	Seizures[1]
Usual onset	Noticeable by age 2[1]
Duration	Lifelong[2]
Causes	Genetic (X-linked dominant)[1]
Diagnostic method	Genetic testing[2]
Treatment	Supportive care, early interventions[2]
Frequency	1 in 4,000 (males), 1 in 8,000 (females)[1]

Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability.^[1] The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled.^[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.^[1] 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.^[5] 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.^[5]

There is no cure.^[2] Early intervention is recommended, as it provides the most opportunity for developing a full range of skills.^[6] These interventions may include special education, speech therapy, physical therapy, or behavioral therapy.^[2][7] Medications may be used to treat associated seizures, mood problems, aggressive behavior, or ADHD.^[8] 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][9]