Fragile X syndrome is a genetic disorder that affects how a person develops, learns, and behaves. People with fragile X syndrome may have intellectual disability, developmental delays, speech and language difficulties, anxiety, attention and hyperactivity problems, and features of autism spectrum disorder.

Fragile X syndrome is the most common inherited cause of intellectual disability. In the United States, it is estimated to affect about 1 in 7,000 males and 1 in 11,000 females. Many children with fragile X syndrome are diagnosed after parents or caregivers first notice developmental delays, often around 12 months of age for boys and 16 months for girls.

Although there is no cure for fragile X syndrome, early intervention, educational support, therapy services, and medications can help manage symptoms and improve quality of life.

Fragile X syndrome is a genetic condition that affects how the brain develops and functions, leading to a range of challenges in learning, behavior, and physical development.

Humans have 23 pairs of chromosomes. The X and Y are the sex chromosomes. Females have two X chromosomes (XX), and males have one X and one Y chromosome (XY). Fragile X syndrome is caused by a mutation in a gene called FMR1 on the X chromosome. This gene produces a protein called FMRP. The FMRP protein is important for building and maintaining connections between nerve cells and the brain, which are needed for learning, memory, and communication. When the body does not make enough FMRP, or makes none at all, the brain’s ability to process information and regulate behavior is affected.

People with fragile X syndrome may have a variety of features that can change as they grow. In early childhood, physical signs are often subtle, and the condition may not be recognized and treated. As children get older, certain characteristics may become more noticeable, such as a long face, large ears, flexible joints, and flat feet. Boys and girls can both be affected, but boys usually have more significant challenges because they have only one X chromosome, while girls have two.

Fragile X syndrome is caused by a mutation in the FMR1 gene on the X chromosome. This gene contains a section where a short DNA sequence, made up of the letters CGG, is repeated a certain number of times. The number of repeats affects how the gene works.

Most people have between 5 and 44 repeats. In fragile X syndrome, the sequence is repeated over 200 times. This large expansion causes the gene to become silenced, meaning it is turned off and usually cannot produce its protein, called FMRP. Without enough FMRP, the brain and nervous system cannot develop and function as they should, leading to the symptoms of fragile X syndrome.

There are different types of FMR1 gene mutations:

• Full mutation: This is the classic form of fragile X syndrome, where the gene is silenced and little or no FMRP is made, leading to the typical features of the condition.
• Premutation: In this form, the CGG DNA sequence is repeated 55 to 200 times. People with a premutation usually do not have fragile X syndrome, but they may have milder symptoms or be at risk for other health problems, such as tremors or early menopause. A premutation can be passed to children and may expand to a full mutation in future generations.
• Intermediate expansion: In this form, the CGG sequence is repeated 45 to 54 times. It usually does not cause symptoms, but it can sometimes be passed on and expand in future generations.

In rare cases, other types of changes in the FMR1 gene can also cause fragile X syndrome, but these are much less common.

The mutation in the FMR1 gene that causes fragile X syndrome is inherited in an X-linked dominant pattern, meaning it can be passed from parent to child through the X chromosome. The risk of the gene expanding from a premutation to a full mutation is higher when passed from mother to child rather than from the father.

Risk factors for fragile X syndrome include:

• Having a mother with a full mutation or premutation in the FMR1 gene (fathers with an FMR1 premutation or full mutation can pass the mutation to daughters but not sons; when passed by fathers, the gene change is passed as a premutation)
• Family history of fragile X syndrome, intellectual disability, or autism spectrum disorder of unknown cause
• Having relatives with fragile X-associated conditions, such as fragile X-associated tremor/ataxia syndrome (FXTAS) or fragile X-associated primary ovarian insufficiency (FXPOI)

Symptoms of fragile X syndrome may include:

• Developmental delays, such as late sitting, walking, or talking
• Intellectual disability, ranging from mild to severe
• Learning disabilities, especially with math and problem-solving
• Speech and language problems, including delayed speech, poor articulation, and repetitive or rapid speech
• Attention problems and hyperactivity
• Anxiety and social difficulties, such as shyness or trouble making eye contact
• Features of autism spectrum disorder, including repetitive behaviors (such as hand flapping), social avoidance, and difficulty with communication
• Sensitivity to sensory experiences, such as noise, light, or certain textures
• Behavioral challenges, including impulsivity, aggression, or self-injury
• Seizures
• Physical features, which may become more noticeable with age, such as a long and narrow face, large ears, prominent jaw and forehead, flexible joints, flat feet, and, in males after puberty, enlarged testicles
• Low muscle tone
• Frequent ear infections
• Strabismus (crossed eyes)
• Mitral valve prolapse (a heart valve problem)
• Obesity and increased appetite in some individuals

The severity and specific features can vary widely from person to person, even within the same family.

To diagnose fragile X syndrome, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests.

Your doctor may ask about your child’s developmental milestones, such as when they began to sit, walk, or talk, as well as any learning difficulties, behavioral concerns, or family history of intellectual disability, autism spectrum disorder, or fragile X syndrome. During the physical exam, your doctor will look for features that may be associated with fragile X syndrome, such as a long and narrow face, large ears, flexible joints, flat feet, or, in males after puberty, enlarged testicles. The doctor may also check for low muscle tone, frequent ear infections, and other medical issues linked to the condition.

Additional tests are necessary to make a diagnosis. They may include the following:

• Genetic testing for the FMR1 gene: This blood test is the main way that fragile X syndrome is diagnosed. Laboratory analysis uses molecular techniques (polymerase chain reaction and Southern blot) to measure the number of CGG repeats in the FMR1 gene and whether the gene is silenced. The test can identify intermediate expansions, premutations, and full mutations.
• Prenatal testing (if indicated): For families with a known risk, prenatal diagnosis can be performed using chorionic villus sampling (testing tissue from the placenta) or amniocentesis (testing the fluid—called amniotic fluid—that surrounds the baby during pregnancy) to analyze fetal DNA for changes in the FMR1 gene.

Routine newborn screening for fragile X syndrome is not currently performed in the United States.

There is no cure for fragile X syndrome, but a combination of therapies, educational support, and medications can help manage symptoms and improve quality of life. Treatment plans are tailored to each person’s needs and may involve a team of specialists.

Treatments for fragile X syndrome include:

• Early intervention services: Programs for infants and toddlers that focus on developing communication, motor, and social skills to give children the best possible start.
• Special education and individualized education programs (IEPs): Customized educational plans that address each child’s strengths and challenges, often including support for learning disabilities and behavioral needs.
• Speech and language therapy: Helps improve communication skills, pronunciation, and understanding of language.
• Occupational therapy: Assists with daily living skills, fine motor coordination, and adapting tasks or environments to the individual’s abilities.
• Physical therapy: Focuses on improving motor control, posture, and balance.
• Behavioral therapy: Teaches coping skills, reduces problematic behaviors, and helps manage anxiety, aggression, or self-injury.
• Medications: Used to manage specific symptoms such as attention problems, hyperactivity, anxiety, mood instability, aggression, or seizures. Medications are chosen based on the individual’s symptoms and are closely monitored by a doctor.
• Family support and counseling: Provides education, resources, and emotional support to families and caregivers, helping them navigate challenges and access services.

People with fragile X syndrome may be at increased risk for certain complications, including:

• Seizures, which are more common in childhood and often resolve as children get older
• Autism spectrum disorder, which can cause additional challenges with communication, social skills, and behavior
• Attention deficit hyperactivity disorder (ADHD), leading to problems with focus, hyperactivity, and impulsivity
• Anxiety and mood disorders, such as excessive worry, depression, or mood swings
• Aggressive or self-injurious behaviors
• Sensory processing difficulties, such as being overly sensitive to noise, light, or touch
• Physical health issues, such as frequent ear infections, flat feet, joint laxity (loose joints), and mitral valve prolapse
• Obesity and increased appetite
• In females with a premutation, increased risk for fragile X-associated primary ovarian insufficiency (early menopause)
• In older adults with a premutation, increased risk for fragile X-associated tremor/ataxia syndrome (a condition causing tremors, balance problems, and memory issues)

The outlook for people with fragile X syndrome can vary widely depending on factors such as the severity of intellectual disability, the presence of additional conditions such as autism or seizures, and the individual’s strengths and challenges. Some people may have mild learning difficulties and be able to live independently, while others may have more significant needs and require ongoing support throughout their lives.

Early diagnosis is important so that children and families can access appropriate support, therapies, and genetic counseling. Most people with fragile X syndrome have a normal life expectancy.

This article was medically reviewed by Elizabeth Jonas, MD, the Harvey and Kate Cushing Professor of Medicine (Endocrinology) and Professor of Neuroscience at Yale School of Medicine.