Sunday, March 27, 2011

The most common inherited cause of mental retardation

What is the most common genetic condition that can lead to mental retardation, or the more modern phrase, “intellectual impairment?” If you thought the answer was Down Syndrome, you would be wrong. The answer is Fragile X Syndrome, a condition that many of us have likely never heard of.

What is Fragile X Syndrome?
The intellectual impairment of FXS can range from learning disabilities to more severe cognitive or intellectual disabilities. There are also speech and behavioral abnormalities.
Males with Fragile X
Approximately 1/4,000 males have Fragile X Syndrome and many of them have never been diagnosed. Males with Fragile X Syndrome almost always exhibit mental retardation. FXS is the most common known cause of autism or "autistic-like" behaviors. Symptoms can also include characteristic physical and behavioral features and delays in speech and language development.
Behavioral characteristics in males include attention deficit disorders, speech disturbances, hand biting, hand flapping, autistic behaviors, poor eye contact, and unusual responses to various touch, auditory or visual stimuli.
Females with Fragile X
The characteristics seen in males can also be seen in females, though females often have milder intellectual disability and a milder presentation of the behavioral or physical features. About a third of the females have a significant intellectual disability. Others may have more moderate or mild learning difficulties. Similarly, the physical and behavioral characteristics are often expressed to a lesser degree. Many girls thought to have Attention Deficit Hyperactivity Disorder (ADHD) actually have FXS.
One well recognized consequence for women who carry the mutation is an increased risk for premature ovarian failure (POF), defined as the cessation of menses before the age of 40. Among women who carry the mutation, approximately 21% have POF compared to only 1% in the general population.
Fragile X Syndrome is an X-linked genetic disease
Why are males far more severely affected than females? This is because the mutation exists on the X-chromosome. (FXS is due to a mutation in the X-linked FMR1 gene). X-linked conditions are more severe in males than females, because males have only a single X-chromosome (males are 46 XY) and females (who are 46 XX) have two. In females, if one X has the mutation, the other X chromosome does not and this can minimize or prevent many of the features of an X-linked condition.
Other common X-linked genetic diseases are hemophilia and color blindness, also much more common in males. Of these conditions, females who carry the mutation are unaffected.
How does someone get Fragile X Syndrome?
This is a genetic disease, and a person is born with it. The Fragile X mutation follows the traditional rules of X-linked inheritance: Half of the children of carrier mothers will receive the mutation. If the father is the carrier of the mutation, none of the sons and all of the daughters will receive the mutation.
Approximately 1/200 females and 1/1,000 males carry the FXS mutation. Also about 4% of males and 8% of females of Northern European descent will carry the mutation.
Is there any treatment?
At this time, there is no cure for FXS. However, special education, speech and language therapy, occupational therapy and behavioral therapies are helpful in addressing many of the behavioral, and cognitive issues in fragile X syndrome. In addition, medical intervention including medications can be helpful for aggression, anxiety, hyperactivity and poor attention span. Because the impact of fragile X is so varied, it is important to do a careful evaluation of the individuals' abilities and difficulties to tailor a treatment plan to address specific needs.
Is prenatal diagnosis available?
Only in the past few years has there been a simple blood test which is an affordable and accurate diagnostic test for a woman to find out if she is carrying the FXS mutation.
In one study, families with a son affected by Fragile X were asked if they knew during the pregnancy that their baby was going to grow up with this condition, would they have chosen to continue the pregnancy.
99% of the families said no. Why is that?
Boys with Fragile X have a common set of behaviors that make them extraordinarily difficult to take care of. Other than sleeping, these kids never stop moving. 16 hours a day, these boys are in motion: running, jumping, tumbling, grabbing, throwing and breaking things. They can’t help it. Year after year this continues, getting far worse during adolescence. Families cannot keep babysitters. Schools expel these kids. These parents are desperate just to have an occasional day off. 95% of the marriages end in divorce. You do not see numbers like this in families whose child has Down Syndrome.
What if someone has the mutation and still wants to have children?
Today’s world offers a near-perfect, but not inexpensive solution for this scenario, called PGD. This stands for pre-implantation genetic diagnosis. The couple goes to an IVF clinic. The fertilized embryos are genetically tested prior to implantation. Only embryos that do not carry the mutation are transferred, so any child born from this process will not carry the mutation.
Some of the above material was obtained from The National Fragile X Foundation. http://www.fragilex.org/html/summary.htm

Other Links
Medicine.net article.

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