Fragile X syndrome is a genetic abnormality on the X chromosome that leads to intellectual disability and behavioral disorders. Diagnosis is with molecular DNA analysis. Treatment is supportive.
Fragile X syndrome is an abnormality of a specific gene locus on the X chromosome and is the most common inherited cause of intellectual disability and autism spectrum disorder (1). Males are more commonly affected than females. (Down syndrome is the most common cause of intellectual disability in males; although it is a genetic disorder, most cases occur sporadically and are not inherited.)
The symptoms of Fragile X syndrome are caused by an abnormality of the FMR1 gene on the X chromosome. The abnormality is an unstable triplet repeat expansion; unaffected people have < 54 CGG repeats and people with Fragile X syndrome have > 200. People with 55 to 200 CGG repeats are considered to have a premutation because the increased number of repeats increases the likelihood that further mutation will result in > 200 repeats in a subsequent generation.
Fragile X syndrome affects approximately 1/4000 males and 1/8000 females (2). The premutation is more common. Females with the disorder are typically less impaired than males. Fragile X syndrome is inherited in an X-linked pattern and does not always cause clinical symptoms in females.
In the past, examination of the karyotype revealed a constriction at the end of the long arm of the X chromosome, followed by a thin strand of genetic material, which was why the syndrome was considered a chromosomal abnormality. However, this structural defect does not appear when modern cytogenetic techniques are used, and this is the reason why Fragile X syndrome is now considered a single-gene disorder and not a chromosomal abnormality.
General references
1. National Fragile X Foundation. Fragile X 101. Accessed August 6, 2025.
2. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. Fragile X syndrome; [updated 2020 Jun 10; reviewed 2020 Apr 1; cited 2025 Jul 29]; [about 5 p.]. Available from: Fragile X syndrome: MedlinePlus Genetics.
Symptoms and Signs of Fragile X Syndrome
People with Fragile X syndrome may have physical, cognitive, and behavioral abnormalities.
Typical features include large, protuberant ears, a prominent chin and forehead, a high arched palate, and, in postpubertal males, macroorchidism. The joints may be hyperextensible, and heart disease (mitral valve prolapse) may occur.
Cognitive abnormalities may include mild to moderate intellectual disability. Features of autism spectrum disorder may develop, including perseverative speech and behavior, poor eye contact, and social anxiety.
Women with the premutation may have premature ovarian failure; sometimes menopause occurs in the mid-30s. Males and females with an FMR1 premutation are at risk of Fragile X–associated tremor/ataxia syndrome (FXTAS), which is associated with gait abnormalities, intention tremors, later intellectual impairment, and psychiatric problems.
Diagnosis of Fragile X Syndrome
DNA testing
Fragile X syndrome is frequently not suspected until school age or, rarely, adolescence, depending on the severity of the symptoms and degree of intellectual disability, unless there is a significant family history. Boys with autism spectrum disorder and intellectual disability should be tested for Fragile X syndrome, especially when they have similarly affected maternal relatives.
Molecular DNA analysis (polymerase chain reaction testing and Southern blot analysis to determine both repeat size and methylation) is done to detect the increased number of CGG repeats (1). A multigene panel that includes FMR1 is available in the United States.
(See also Next-generation sequencing technologies.)
Diagnosis reference
1. Spector E, Behlmann A, Kronquist K, et al. Laboratory testing for fragile X, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(5):799-812. doi:10.1038/s41436-021-01115-y
Treatment of Fragile X Syndrome
Supportive measures
Early intervention, including speech and language therapy and occupational therapy, can help children with Fragile X syndrome maximize their abilities.
Stimulants, antidepressants, and antianxiety (eg, sertraline) medications may be beneficial for some children (Stimulants, antidepressants, and antianxiety (eg, sertraline) medications may be beneficial for some children (1).
Treatment reference
1. Protic D, Hagerman R. State-of-the-art therapies for fragile X syndrome. Dev Med Child Neurol. 2024;66(7):863-871. doi:10.1111/dmcn.15885
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