What is Fragile X Syndrome (FXS)?
Fragile X Syndrome (FXS) is a genetic disorder caused by changes in the FMR1 gene. This gene makes a protein needed for your brain to properly develop. A defect in the gene makes your body produce too little of the protein, or in some cases none at all. When a small part of the gene code is repeated on the X chromosome it causes problems in development.
Each person is born with 23 pairs of chromosomes, or 46 individual chromosomes. The X and Y sex chromosomes determine whether a person is born male or female. Typically females have two X chromosomes, and males have one Y and one X. Because females have two X chromosomes, if they inherit an abnormal FMR-1 gene they still have an unaffected X chromosome remaining. This makes them less affected by fragile X than males who only have one X available. When affected, females tend to have less severe symptoms than males.
Causes of Fragile X Syndrome:
FXS is the most common cause of inherited mental impairment. The mutation that causes FXS is a genetic “glitch” or “stutter”, in which a small section of the genetic material within the gene is repeated too many times. People without FXS have roughly 5 to 40 repeats of this section of the gene, but people with FXS have more than 200 occurrences which is considered a full mutation. With full mutation, the gene is turned off and no longer produces the protein it is intended to make. This protein is found primarily in nerve cells, and scientists believe it helps with brain development.
When an individual has 41 to 58 repeats, which is called the gray zone, the number of repeats can increase when passed from a parent to child. Though these parents are typically not at risk of having a child with FXS, the repeats can increase with each generation and therefore the grandchildren might be at risk.
Adults with 59 to 200 repeats of the gene are typically carriers of the FXS gene mutation. If FXS is noted in the family genealogy, DNA testing can determine if a person is a carrier. Roughly 1 in 250 women, and 1 in 800 men, are carriers of the premutation. However, only women with the premutation are at risk of passing on the fragile X syndrome.
Risk Factors For Fragile X Syndrome:
A woman with a premutation has a 50 percent chance of passing the abnormal gene on with each pregnancy. Children receiving the gene from the mother may have premutation or potentially full mutation.
A father with a premutation passes it on to all of his daughters but to none of his sons. The daughters will generally have no symptoms, but will become carriers of the premutation that can then be passed on to their own children. Their sons will not receive the premutation because they only receive the Y chromosome from the father. Men with a full mutation typically are not able to reproduce.
Symptoms of Fragile X Syndrome:
Children with symptoms have many mental and physical symptoms ranging from mild to severe. Most children with FXS do not have serious medical problems and will generally live a normal life span.
Common mental symptoms include:
- Intellectual disability
- Learning problems
- Anxiety and mood issues
- Delays learning to walk or talk
- Autistic-like behaviors such as hand flapping or biting
- Behavior issues, such as focusing and frequent tantrums
- Sensitivity to light, sounds, or touch
- Poor social skills
Common subtle physical symptoms include:
- Large ears
- Large head
- Prominent forehead and chin
- Long and narrow face
- Overly flexible joints (such as the fingers)
- For males, enlarged testicles developing after puberty
Diagnosis of Fragile X Syndrome:
FXS is diagnosed through DNA blood tests. Testing can be conducted to determine if a mutated gene exists leading to fragile X in a child. Once diagnosed the family can begin properly treating behavior and mental disability problems.
Prenatal tests can determine whether the baby of a carrier mother has inherited a full mutation of premutation. This test is called amniocentesis and chorionic villus sampling (CVS). When a CVS test cannot determine between a large premutation versus full mutation, a follow-up amniocentesis may be recommended.
Treatment of Fragile X Syndrome:
There is no cure for FXS, however, there are treatments available to help children and adults with FXS develop important skills and live a long life. There are physical therapy services to assist with walking, talking, and physical interaction. Behavior problems can be managed with the help of certain medications such as antidepressants, stimulants, antipsychotics, or antiseizure drugs.
Getting your child’s school involved is important in helping your FXS child get the support they need. Be your child’s advocate and work with teachers, healthcare providers, therapists, and family members.
Additional Fragile X Resources:
The National Fragile X Foundation provides information on FXS regarding treatments, therapies, and intervention to assist children in becoming an active member of the family, school, and community.
FRAXA Research Foundation supports families affected by FXS and raises awareness of the relatively unknown disease.
Centers for Disease Control and Prevention is a reliable online source for health related information such as data or statistics, emergencies and disasters, healthy living, and diseases and medical conditions.
March of Dimes - leading nonprofit organization for pregnancy and baby health. With chapters nationwide, the March of Dimes works to improve the health of babies by preventing birth defects, premature birth and infant mortality.
Mayo Clinic is a nonprofit worldwide leader in medical care and research for people from all walks of life. Their mission is to inspire hope and contribute to health and well-being by providing the best care to every patient through integrated clinical practice, education and research.