Sunday, June 25, 2017

Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, or mental retardation. FXS occurs when there is a mutation in the FMR1 gene. This gene normally produces a protein the body needs for the brain to develop. The change in the gene causes the body to produce only a little of the protein or none at all, which is what causes the symptoms of Fragile X.

According to the CDC, Fragile X occurs in 1 out of every 4,000 boys and 1 out of 6,000 to 8,000 girls.


Fragile X is passed down from parents to their children. Even if the parents do not have the syndrome, they can have children who do have it. When parents do have it, the mutations in their children can be more serious.

The FMR1 gene is found on the X chromosome. Males and females have at least one X chromosome, so both a mother and a father can pass on the mutated gene to their children. A father with the altered gene will only pass the mutation to his daughters, as Y chromosomes produce only sons. Daughters of men who are carriers will likely be normal; however, they risk having children affected by FXS. A mother can only produce X chromosomes, so she may pass it to her sons or daughters.

The mother of a child with an FMR1 mutation is almost always a carrier of a pre-mutation or a full mutation. The FMR1 altered gene can be passed without symptoms and many people are unaware they have it. A pre-mutation (does not have the syndrome but might have Fragile X- associated disorders) form can be passed without anyone showing any signs or symptoms; however, with each generation, the chances increase for the pre-mutated gene to expand and become a mutated gene, which will increase the symptoms. Note that the severity of symptoms in one child does not mean other children will have more or less severe symptoms.

Signs & Symptoms

The signs and symptoms vary, so it’s very hard to diagnose. The mean age at diagnosis is 32 months. There may be developmental delays in crawling or walking, hyperactive behavior, hand clapping or hand biting. Adults with FXS may have problems with tremors or coordination, while women may experience premature menopause or have difficulty in becoming pregnant.

There are certain patterns:

  1. Intelligence: males have an average IQ of 40; females may have a normal IQ but may demonstrate learning disabilities in academics.
  2. Physical: longer face or jaw, large ears, loose, flexible joints, flat feet, low muscle tone. Some physical symptoms may be present at birth, while others may not develop until after puberty.
  3. Social & Emotional: social anxiety, lack of eye contact, fast, choppy speech, easily upset and distressed by unexpected changes in routine, self-injurious behaviors. Hormonal changes can increase symptoms. According to the National Institutes of Health, one-third of males demonstrate aggressive behavior.
  4. Speech & Language: mild stuttering, language delay and may not speak until two or three years of age. Males may repeat themselves, have trouble in expressing themselves or understanding facial clues such as tone of voice and body language. Females usually have average vocabulary and grammar skills, but their social anxiety and shyness may prevent them from communicating well.
  5. Sensory: hypersensitive to sensory stimuli such as certain sounds and textures, and problems with balance and coordination.

Disorders Associated with Fragile X

Autism: Present in about 30% of people with Fragile X. Most males and one-third of females demonstrate Autism-like features such as flapping hands and repetitive actions.

ADHD/ADD: Almost 90% of males and 45% of females with Fragile X also have ADHD or ADD.

Seizures: Approximately 20% experience seizures.

Pervasive Developmental Disorder – Not Otherwise Specified: About 20 to 30% of people with Fragile X also have PDD-NOS.


There is no cure for Fragile X. There is also no definitive, single treatment for its’ symptoms. There are a variety of therapies and medications which are often used to minimize symptoms.
Recently, the drug trial for arbaclofen came to an end which has caused outrage among some parents who saw positive results in their children who were taking the medication. Research continues to help find a therapy or medication which will help lessen the effects of Fragile X. One of the problems in finding a drug to help with the effects is that the symptoms and behaviors vary widely among individuals with FXS.

Early intervention is very important. A child’s brain is still forming, so a child is more capable of learning. It is recommended that any child who presents with developmental delay, borderline intellectual disabilities, or has a diagnosis of autism, should undergo molecular testing for FXS. Even if a child hasn’t been diagnosed with FXS, he/she may be eligible for services.


Genetic testing is used to diagnose this disease. It was reported in a February 2003 issue of Pediatrics that of those surveyed, 24% of families with a child who was diagnosed with Fragile X, had seen a health care provider ten times before Fragile X testing was performed.

There are three types of tests currently used to diagnose FXS:

  1. DNA molecular test [Southern Blot, and Polymerase Chain Reaction (PCR)]
  2. Chromosome test
  3. Protein test


Genetic counseling is recommended for all families who are affected or at risk of having a pre-mutation or an offspring with a full mutation. Genetic counseling can provide information regarding the inheritance pattern. Prenatal testing can be performed by amniocentesis or CVS to determine if a fetus has inherited the gene.

In 1991, researchers funded by the National Institute of Child Health & Human Development (NICHD) discovered the gene that causes Fragile X. Scientists continue to work on treatment and prevention.

There are nearly 30 Fragile X Clinics located across the country which provide those affected by FXS an evaluation and recommendations for treatment. They also provide medical services and therapies. To learn more about the Missouri clinic, visit the University of Kansas Medical Center's website

Molecular DNA testing is offered in Missouri both at the Cardinal Glennon Children's Hospital in St. Louis and at the Autism Center at the University of Missouri Health Care Children's Hospital in Columbia.


Parent Category: News