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Center for the Study of
Inherited Neurological Disorders

Report on 3rd International Chromosome 9 Workshop

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The genetic implications of tuberous sclerosis are justifiably one of the core concerns of TS families and individuals. Most NTSA member families know that there are two TS genes in the human genome, one each on chromosomes 9 and 16. It is also widely known that the TS gene on chromosome 16 was located in 1992, and current research is dedicated to finding the location of the gene on chromosome 9. However, it is even more difficult to figure out the personal implications of the genetic aspect and the ongoing research. Below, geneticist Dr. Susan Black addresses the question of whether a TS individual can have a healthy family.

What is the probability of a TS adult having a child with TS?

If an adult has tuberous sclerosis, the risk in each pregnancy of having an affected child will be 50%. However, the expression of the disease manifestations may vary from clinically very severe to a milder expression. Although we know that approximately one third each of the TS population fall into the mild, severe, and in between categories, there is no way to predict how severely your child will be affected.

Is there a way to know before birth whether a baby has TS?

At present, a high resolution ultrasound can be performed in the second to third trimester. While doctors can look for tumors in the heart or brain in late pregnancy, a normal ultrasound will not rule out the diagnosis. However, within the next few years, DNA testings will allow for more accurate diagnosis. Under this procedure, chronionic villus sampling (CVS takes samples of cells from the fetus) or amniocentesis (draw out fluid from amnionic sack) will be performed to extract fluids for examination. Doctors will then use the samples to determine whether the TS gene mutation has passed down to the fetus. Since we've only identified the TS gene on chromosome 16, the test will not work for those with mutations on the chromosome 9 gene until its location is found. Fortunately, intense research is on-going to pin point that gene, and it is optimistically predicted that the gene will be found in the next year. This test will also be convenient for diagnosing siblings and other family members who currently have to undergo clinical examinations to receive a probable diagnosis.

If the mother has TS, what options are available to insure a healthy child?

One option for individuals with TS is to use a donor egg with a known or anonymous egg donor. The mother would have embryos (from the donor's unaffected eggs and her husband's sperm) placed into her uterus which would become the gestational carrier. In most anonymous egg donor programs, the donor is screened to rule out as many genetic diseases as possible. DNA testing will add the possibility of using family members as donors. In situations where the donor has been screened and has accepted, the risk of birth defects in any pregnancy remains that of the general population, three to four percent. Assuming that DNA analysis is possible, the other option is to have a CVS or amniocentesis done and make decisions about whether to continue the pregnancy after the diagnosis. For those who are not comfortable with abortion, adoption of a child is an option as well.

If the father has TS, what options are available to insure a healthy child?

He has the option of using a donor sperm to avoid the risk of an affected child. Again if prenatal testing of DNA is available, his wife can undergo CVS or amniocentesis to find out whether the fetus is affected.

If both parents have TS, what is the probability of having an affected child?
In such cases, the risk of affected offspring is 75% in each pregnancy: 50% of carrying a single TS mutation and 25% of having a double dose of the TS gene mutation. Again, donor gametes (eggs and sperm) with the woman being the gestational carrier is an option to insure a non-affected child.

What is gene therapy and will it be possible in the near future?

Gene therapy is an ability to replace the gene that is not working well during the pregnancy. At present, this treatment is being tried in some inherited immune deficiency diseases. There has been success in clinical trials with cystic fibrosis, but work continues. A breakthrough may occur quickly, but it is more likely that we are looking at 10-20 years ahead for diseases like TS.

What are the hot topics in TS genetic research?

Much of the work is now trying to find the gene responsible in chromosome 9, as well as treatment options for clinical manifestations. Most research is either to identify an etiology (cause of TS, how defective gene translates into defective product causing tubers) to allow accurate diagnosis of TS, to evaluate treatment options, and to correlate, if possible, the clinical manifestations with the mutations caused by the gene.