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.

Sunday, March 6, 2011

Early Detection of Ovarian Cancer

In 2010, over 21,000 women were diagnosed with Ovarian Cancer, and almost 14,000 women died from it. Three out of four women who are newly diagnosed with ovarian cancer will already be in Stage 3 or Stage 4, and only 25% of these women will be expected to live 5 more years. Furthermore, there are almost no specific symptoms for ovarian cancer. This is why ovarian cancer is so scary to so many women.
Diagnosis of Ovarian Cancer
Currently, the only way to diagnose ovarian cancer is to undergo abdominal surgery. There is no biopsy for ovarian cancer. Imaging studies lead to suspicion for cancer, but they cannot make the diagnosis. Due to the risks of surgery, avoiding unnecessary surgery is very important when attempting to diagnose early ovarian cancer. Knowing who to operate on and who to watch closely is a challenge for the ob/gyn physician.
Is there a way to screen for ovarian cancer?
Women know that a pap smear is an excellent way to screen for cervical cancer. Why is that? Because abnormal cells on a pap smear can be identified, leading to simple yet effective treatment that will prevent cervical cancer from developing. This is the ideal screening test.
A mammogram is a very good screening test, but not as good as a pap smear. Why? Because a mammogram will still diagnose cancer rather than finding a treatable precancerous condition. But, breast cancer can be diagnosed in a very early state, Stage 1, leading to less invasive treatments and very good long-term survival. Also, many women check themselves for breast lumps, leading to another method for diagnosing early stage breast cancer.
Unfortunately, there is still no pap smear or mammogram equivalent for the early diagnosis of ovarian cancer. The key for women is early suspicion. This is how we can diagnose ovarian cancer at an earlier stage.
Could these vague symptoms actually be due to Ovarian Cancer?
Is ovarian cancer a silent disease, one that shows up without any warning? Perhaps not. In one study of woman diagnosed with ovarian cancer, 70% of women had symptoms for up to 3 months prior to being diagnosed. Further studies have identified symptoms that might be due to early ovarian cancer. These are: increased abdominal size, bloating, feeling full easily, increased urge to urinate and pelvic discomfort or pain. If these symptoms occur 12 or more times in one month, the chances are still very low that these symptoms are due to cancer, but seeing the doctor is advisable.
What about using routine vaginal ultrasound?
Many studies have been done to using routine vaginal ultrasound as a way to diagnose early ovarian cancer. The results have been disappointing. In some studies, hundreds of women were identified as possible ovarian cancer and underwent surgery. Only 1% actually had cancer. In one study of 10,000 women, 300 underwent surgery. One woman had ovarian cancer, and one died from complications of surgery.
What about the CA 125 test?
CA-125 has been around for over 15 years. Gildna Radner (1946-1989), a famous comic and wife of Gene Wilder was diagnosed with ovarian cancer in 1985. It took almost a year before doctors made the diagnosis. Despite aggressive treatments, she died in 1989. Her name is often linked to the CA 125 test. If only they had done this test, they might have diagnosed her cancer sooner!
The reality is much more frustrating. We know a lot about CA 125. It is called a tumor marker, a chemical in the blood associated with the presence of cancer in the body. CA 125 is elevated in 80% of women with ovarian cancer (which means it is negative in 1 out of 5 women who have ovarian cancer). Unfortunately, CA 125 is elevated in many other conditions including endometriosis, fibroids and colon diseases like inflammatory bowel disease. Further, it is often elevated in women prior to menopause for no reason at all. Therefore, CA 125 is NOT considered a useful screening test for ovarian cancer.
A new test – the OVA1
Researchers have been looking for years for a better blood test that the CA 125. Recently, the FDA-cleared OVA1 test has become available. This test measures five different chemicals in the blood, one of which is the CA 125. It has not been approved as a universal screening test, however. The OVA1 can only be done if the patient has an ultrasound showing an enlarged ovary or an ovarian cyst. The test can help the doctor determine whether the chances are low or high that the cyst is actually a cancer.
Conclusion
There is still no FDA approved screening test for ovarian cancer. Routine ultrasound and routine CA 125 testing for low-risk women has not resulted in improved diagnosis. Women need to be aware of the combination of common symptoms that can sometimes be caused by early ovarian cancer. Your gynecologist has an array of blood and imaging tests available that often will be able to reassure you that your situation is benign and that surgery may not be necessary.
*portions excerpted from the March 2011 Committee Opinion of the American College of Ob/Gyn, Number 477.