Fragile X syndrome (FXS) is an inherited condition that can cause numerous birth defects. It involves a gene abnormality on the X chromosome that may be transmitted from a mother or father at the time of conception. 

FXS can cause cognitive impairment that ranges from learning disabilities to mental retardation and autism. It can cause behavioral problems, such as lack of attention and hyperactivity (e.g., attention-deficit hyperactivity disorder). Autistic-like symptoms, such as poor eye contact and social skills, and repetitive body movements (e.g., hand-flapping), are also common.

Physical characteristics of FXS include prominent ears, an elongated face and enlarged testicles (after puberty).

FXS affects males more often and more severely than females. It is the most common cause of mental retardation in boys, and it is a significant cause of mental retardation in females. Parents who suspect their child has FXS, or anyone with a family history of unexplained mental retardation, should contact a physician for screening.

The syndrome can be diagnosed with a DNA analysis. This test can be performed on children and adults, as well as prenatally. It can also identify people who are carriers. Carriers of FXS may not display symptoms of the syndrome, but possess the abnormal gene and are at risk of transmitting it to their offspring. They are also at risk of developing certain complications, including intentional tremors (shaking that occurs during activity but not at rest) and fertility issues.

There is no specific treatment for FXS. Therapies designed to help maximize the potential of a child with FXS include speech language therapy, occupational therapy and various medications to treat disorders associated with the syndrome. In general, the amount of care required will depend on the severity of a child’s symptoms.

Once a child has inherited the abnormal gene that causes FXS, there is no way to prevent the condition or its symptoms.

Fragile X syndrome (FXS) is a genetic condition that produces a number of different birth defects. It can cause cognitive impairment (e.g., mental retardation), emotional and behavioral problems (e.g., attention-deficit hyperactivity disorder), as well as distinctive physical characteristics (e.g., prominent ears, elongated face, enlarged testicles after puberty).

FXS occurs due to a genetic stutter on the fragile X mental retardation 1 (FMR1) gene. This gene is located on the X chromosome, which is one of two sex-defining chromosomes that children inherit from their parents.

A section of DNA in the FMR1 gene includes a certain sequence of nucleotides (building blocks of DNA): cytosine, guanine and guanine (CGG). Normally, this sequence repeats approximately 30 times. When the CGG sequence is repeated too many times (more than 200 times), a certain protein (fragile X mental retardation protein, FMRP) fails to be made. A lack of this protein triggers FXS. It is not clear exactly why this happens, although FMRP appears to affect communication between nerve cells in the brain.

FXS involves an abnormality in a single gene on a particular chromosome. Thus, it is different from Down syndrome, in which an extra chromosome is present. It is called “fragile” X syndrome because when the X chromosome is viewed under a microscope, the area with the mutation looks as if it is barely connected to the rest of the chromosome.

FXS affects males more severely than females because the gene mutation is located on the X chromosome. Males have only one X chromosome, which they inherit from their mother, whereas females have two (one from each parent). Females that inherit an X chromosome with the mutated gene may offset its effects by having a second chromosome with a normal (non-mutated) FMR1 gene. Thus, females with FXS are more likely to have less severe symptoms than males with the syndrome.

FXS occurs in about one in every 4,000 male infants and around one in every 8,000 female infants, according to the National Institutes of Health. It is the most common cause of mental retardation in boys, and it is a significant cause of mental retardation in girls. FXS can also cause autism in affected children.

Approximately 20 percent of children with FXS develop seizures, according to the March of Dimes. Children with FXS may be at increased risk of sinusitis, otitis media, vision problems and digestive disorders.

Fragile X syndrome (FXS) occurs due to an abnormality in the fragile x mental retardation 1 (FMR1) gene, which is located on the X chromosome. The abnormality involves a section of DNA where the nucleotides (building blocks of DNA) cytosine, guanine and guanine (CGG) are repeated too many times. Normally, this CGG sequence is repeated approximately 30 times.

Depending on the number of CGG repeats, people are either deemed to be FXS carriers or have a full mutation of FXS:

• Carrier state (also called premutation of the FMR1 gene). This may involve between 50 and 200 CGG repeats. Men and women can be carriers, although this occurs more often among women. Estimates vary, but it appears that one out of every 250 women and one out of every 700 men are FXS carriers. When the abnormal FMR1 gene is transmitted from female carriers to their children, the number of CGG repeats increases, such that children may inherit the full mutation of the gene. CGG repeats do not increase when transmitted by male carriers.
  
  For carriers, symptoms of FXS may be insignificant, although attention or learning deficits, increased shyness and a risk of depression may be present. In addition, the following complications may occur in FXS carriers:
  
  
• • Fragile X-associated tremor ataxia syndrome (FXTAS). This is an adult-onset condition that involves progressive intention tremors (shaking that occurs during activity, but not during rest), ataxia (balance or gait problems) and cognitive decline (including short-term memory loss). This is more common in males FXS carriers than in female carriers. It is unknown exactly how many carriers are affected by FXTAS. It typically occurs in men 50 years and older, and symptoms usually progress slowly. FXTAS is sometimes misdiagnosed as Parkinson’s disease.
    
    
  • Fertility issues. Female FXS carriers are at risk of developing fragile X-related premature ovarian failure (POF). This affects ovarian function and can lead to infertility and early menopause (menopause that occurs prior to age 40). It may also increase the rate of twin births. However, this risk applies only to carriers and not to women with the full mutation. Estimates vary, but less than one-third of female carriers experience POF and early menopause.
    
    
• Full mutation of FMR1 gene. This involves having more than 200 CGG repeats on the FMR1 gene. This is the version of the condition that usually causes symptoms of FXS. Most males with full mutation exhibit symptoms of FXS. Women with full mutation may have no significant effects, although one-third to one-half of females with the full mutation will exhibit symptoms of FXS, according to the March of Dimes. Because females have two X chromosomes, the non-mutated chromosome may compensate for the one with a full mutation, reducing the severity of FXS symptoms.  

Fragile X syndrome (FXS) is caused by a mutation of the fragile x mental retardation 1 (FMR1) gene, which is located on the X chromosome. Children may inherit the abnormal gene from their mother, father or both parents. Parents can carry the abnormal gene that causes FXS but display no symptoms of the syndrome and, thus, unknowingly transmit it to their children. 

Boys are at greater risk of FXS than girls. Boys who receive the mutated gene from their mother usually develop a full-blown case of FXS – since boys have only one X chromosome, which they inherit from their mother. On the other hand, girls have two X chromosomes (they receive one from each parent). A second X chromosome in girls may compensate for, or reduce the effects of, an inherited X chromosome with an abnormal FMR1 gene.

The genetic transmission of FXS is different from other x-linked defects such as hemophilia. In FXS, both males and females can be carriers of the defective gene or be affected by the gene. In contrast, hemophilia is only transmitted from mother to son.

In addition, children who inherit the gene from their mother are at greater risk of FXS than children who inherit the gene from their father. The FMR1 gene mutation can worsen when it is transmitted from a woman to her child. Thus, a woman who is a carrier but has no symptoms of FXS can give birth to a child with full-blown FXS. On the other hand, the mutation does not worsen when it is transmitted from a man to his daughter. Thus, an asymptomatic (without symptoms) male who carries the faulty gene may pass it to his daughter, who may, in turn, become an asymptomatic carrier. Although she may not develop FXS, the daughter is at risk of giving birth to children with FXS.

Signs of fragile X syndrome (FXS) can range from mild to severe, and some symptoms may not appear at all in children with FXS. For example, most males with FXS have mental retardation, whereas about half of all females with FXS have mental retardation. In general, females tend to have milder symptoms than males – such as learning disabilities and behavioral problems (e.g., social anxiety, mild attention-deficit hyperactivity disorder) rather than the profound cognitive impairment in mental retardation.

Many children with FXS also have autistic-like symptoms (e.g., little eye contact, repetitive movements, poor social skills). Estimates vary, but it appears that as many as one-third of all children with FXS are also diagnosed with autism, according to the National Fragile X Foundation (NFF). Of the various physical signs that may indicate FXS, prominent ears, an elongated face and enlarged testicles (after puberty) occur in 60 percent of all cases of FXS, according to the NFF.

FXS may be difficult to identify in infants. Very few signs are apparent during the first year of life, with the exception of a large head circumference in some patients. For parents, the most noticeable indication that something may be wrong with their child occurs when they notice delays in basic development (e.g., taking longer than normal to walk and talk).  

Cognitive signs of FXS may include:

• Learning disabilities
  
• Delayed speech or language development
• Mental retardation

Behavioral signs of FXS may include:

• Autistic-like behaviors
  
• • Avoids eye contact
    
  • Odd, repetitive movements (e.g., hand-flapping, hand-biting)
    
  • Tactile defensiveness (negative response to touch)
    
  • Sensitivity to sound or light
    
  • Temper tantrums
    
  • Speech disturbances such as perseverative speech (continued repetition of words or phrases) or cluttering (abnormal rate of speech combined with attention deficits)
    
    
• Hyperactivity
  
• Inability to concentrate
  
• Shyness
  
• Social anxiety

Physical signs of FXS may include:

• Prominent ears
  
• Enlarged testicles (macroorchidism) after puberty
  
• Elongated face
  
• Large body size
  
• Large head (macrocephaly)
  
• Prominent jaw
  
• Finger joints that can extend beyond the normal range (e.g., double-jointed)
  
• Flat feet
  
• Mitral valve prolapse (heart deformity characterized by heart murmurs)

Parents who believe their child has FXS should consult their child’s pediatrician. Anyone with a family history of unexplained mental retardation should see a physician for FXS screening, especially if they are considering having children.

It is difficult to identify fragile X syndrome (FXS) based on signs or symptoms alone. The signs of FXS can differ significantly from child to child, and symptom severity may range from insignificant to profound. If parents suspect their child has FXS, they should report all signs or symptoms to their child’s pediatrician. A physician will likely compile a medical history and may perform a physical examination of the child. However, the only way to determine the presence of FXS is through a DNA analysis. This may also be used to identify asymptomatic (without symptoms) carriers (both male and female).   

DNA analysis has been available since 1991. It can accurately and reliably identify the gene mutation responsible for FXS in children and adults. The analysis can be performed with a small sample of blood, skin, bone or tissue.

Prenatal DNA testing may also be performed. This can identify whether a fetus has inherited a full mutation of the gene, but cannot always identify whether the child will be born with mental retardation. Prenatal DNA tests can be performed in the following ways:

• Amniocentesis. A hollow needle is inserted into a pregnant woman’s abdomen, and a sample of amniotic fluid from around the developing fetus is removed and analyzed.
  
  
• Chorionic villus sampling. Vaginal removal of a small sample of the placenta (protective tissue that nourishes a fetus) for analysis.

DNA analysis has replaced previous FXS diagnostic tests, such as karyotyping (looking for abnormalities by examining images of matched pairs of chromosomes). The chromosomal analyses are not sensitive enough to detect mutations in the gene responsible for FXS. Thus, DNA analysis is preferred for its reliability, accuracy and ability to identify asymptomatic carriers as well as people with the full-blown syndrome.

There is no cure for fragile X syndrome (FXS). Treatment is generally aimed at helping children with FXS achieve their highest possible potential and improving their quality of life.

Children with FXS have a normal life expectancy. Their treatment needs depend on the severity of their symptoms, especially the level of cognitive impairment, if any. Children with profound mental retardation as a result of FXS may need supervised care for the rest of their lives. However, children with FXS whose cognitive impairment is limited to learning disabilities may require special education and be able to live independently and function well in society as adults.  

Some therapies used to help improve the quality of life for children with FXS include:

• Speech language therapy. Therapy designed to improve a child’s ability to communicate. This may include alternate forms of communication, including American Sign Language or the use of images to represent objects (e.g., food, toys) or activities.
  
  
• Occupational therapy. Therapy that helps impaired people perform daily activities, and may focus on developing fine motor skills. This can include sensory integration (which involves the gradual exposure to stimuli) in an attempt to calm hyperactive children.
  
  
• Behavior therapy. A type of conditioned learning in which desired behaviors are reinforced through the use of rewards.
  
  
• Medications. Various types of drugs are available that may help treat seizures or various disorders associated with FXS, such as attention-deficit hyperactivity disorder (ADHD), aggression, depression, anxiety or mood instability.

Having a child with FXS can be extremely stressful for parents. Parents are encouraged to seek emotional support through a variety of methods, including friends, family, counselors and/or support groups.  

Once a baby has inherited the gene abnormality responsible for fragile X syndrome (FXS), there is no way to prevent the condition or its symptoms.

Prior to conceiving a child, parents can have genetic testing performed to identify whether either parent is an FXS carrier and determine the likelihood of conceiving a child with the condition. A physician may take a detailed family history before performing DNA tests that can help identify whether a man or woman is a FXS carrier. Depending on the outcome, a couple may opt not to have children to avoid having a child with FXS.

If a person is identified as an FXS carrier, other members of their family should also be tested, since their children may be at risk. For example, a male carrier will transmit the gene mutation to all his daughters (who themselves become carriers). These women are then at risk of having children born with the full-blown syndrome. Thus, a woman identified as a carrier may have sisters who are also carriers and who may also have children with FXS.

Preparing questions in advance can help patients and parents have more meaningful discussions with their physicians regarding their or their child’s treatment options. The following questions related to fragile X syndrome (FXS) may be helpful:

1. To my knowledge, no one in my family has FXS. Do you recommend genetic testing to see if I’m a FXS carrier?
   
   
2. Could I be an FXS carrier and not show any symptoms of the condition?
   
   
3. A member of my family has a child with mental retardation. Could FXS be the cause? If so, does that mean I could be a FXS carrier?
   
   
4. How is genetic testing for FXS performed?  How do we prepare for this test?
   
   
5. If I’m a carrier of FXS, should others in my family be tested as well?
   
   
6. What are the chances that my partner and I will have a child with FXS?
   
   
7. I’m pregnant. Do you recommend DNA testing to identify whether my child will have FXS?
    
8. Why is it important to identify FXS as the cause of my child’s mental retardation?
   
   
9. What signs should I look for in my infant or toddler that may indicate FXS?
   
   
10. What treatments do you recommend for my child’s FXS symptoms?