Topic: “Reproductive Decision Making”
Thursday, January 29, 2015
Presenter: Jennifer Glass, Genetic Counselor at the TS Clinic in Cincinnati
Introduction by Mark Martin, Head of the TS Adult Task Force
- Jennifer Glass licensed genetic counselor
- Specializes in genetic research
- Has worked closely with the TS Alliance and assisted with the Consensus Conference and the TS
World Conference this past July
Basic Family Planning/Reproductive Decision Making as it relates to Tuberous Sclerosis
First step in Family Planning
- First decide if you want to have kids
Traditional Conception
- If you or your spouse have TSC mutation there is a 50/50 chance that your child will also have a
TSC mutation with each conception
- Need to tell your OBGYN if one of the parents has TSC
- Noninvasive procedures to check the fetus for TSC
 Fetal echo: ultrasound of the heart
 Fetal MRI: recently done at Cincinnati, just like a regular MRI, looking for signs of TSC
 Not finding a sign does not mean that TSC is not present, but lessons the chance
 If find signs, much more convinced that the baby may have TSC
 Evaluation at birth
Non Biologic Option
- Adoption
 Domestic Adoption within the United States can be either public or private
 International Adoption
 Different pros/cons for both
- Egg/Sperm Donation
 Cheaper and easier if it the dad with the TSC mutation, since sperm donation is less
complicated than egg donation, but both are possible
Prenatal Testing Options
- CVS: chorionic villus sampling
 Chorionic is what turns into the Placentia
 Done at 10-12 weeks of pregnancy
 Takes a sample of the Placentia so that it can be genetically tested for the mutation found in
the parent
 A small catheter is threaded in through the cervix to the uterus and gets a biopsy of the
Placentia
 Can test it for the known mutation
 Only done by a trained OBGYN and they should be keeping track of their complications
-
-
 Risks are a little bit higher, but still in the 1% or less range
Amniocentesis
 Done after 15 weeks of pregnancy
 Skin cells shed by the baby and genetically test those cells for the mutation found in the
parents
 Take a long needle go through the woman’s belly and into the amniotic fluid and remove
some of the amniotic fluid that contains some of the babies skin cells
 Simpler procedures and the risks are lower, around 1 in 800.
In both options, have to know the mutation that is causing TS in the parent
PGD: Preimplantation Genetic Diagnosis (using IVF)
- Starts like traditional IVF where they collect eggs from mom, and sperm from dad, mix them
together is a petri dish and grow an embryo to either a 3 or a 5 cell stage.
- Goal is to have multiple embryos and take a small biopsy cell from each of those embryos
- Biopsy can be sent off to a lab and look for the known mutation in TSC 1 or TSC2
- Goal is to implant only the embryos that do not have TSC gene.
- Screen for TSC before pregnancy
- IVF is expensive and complicated, no guarantee to get pregnant and on average take about 3
cycles to get pregnant.
- Sometimes covered by insurance, depends on individual plans
Each option is going to be better for a different family
- Genetic Counselor is to give you all the options
- It is up to each individual which option is best for them
Women with TSC
- Woman with TSC thinking about carrying pregnancy themselves need to check with TSC provider
prior to getting pregnant
- TSC Manifestation that can exacerbated during pregnancy
 LAM (lung Problems)
 Renal AML aggravated by the extra hormones that are seen during pregnancy
 Some seizure Medications may not be the best medication to be on when pregnant (may
need to change medications)
 Never going to say someone can’t get pregnant, but recommend checking in with your
doctor first to make sure all screening is up to date and it is safe to go into the pregnancy.
Questions:
Question: Finding the genetic Defect of parent, what are the different ways it can be done?
 Two known genes that can cause TSC: TSC1 and TSC2
 In the past there was only one lab (Athena Diagnostics). But thanks to a recent Supreme
Court ruling there are now many labs (at least a dozen labs in the United State) that offer
genetic testing for TSC
 Currently a full genetic analysis would include sequence analysis and deletion analysis of the
TSC1 and the TSC2 gene (4 total test)
 When all four test are done the detection rate is about 85%, and may be going up a little bit
in the near future




Can be ordered by geneticist, genetic counselor or even some neurologist or other
physicians familiar with TSC
If you do not have a professional to order an assessment you can search for a genetic
counselor on the website for National Society of Genetic Counselors www.nsgc.org scroll to
the bottom and search for a counselor close by you
The Genetic Counseling is not perfect and still may not find the mutation, but for most
people they will be able to find the mutation.
Once the mutation is found it opens up some additional options such as prenatal testing and
PGD testing
Question: How far would you say we have come in the genetic accuracy with the test and who is using
it?
- When genetic testing first became available, it was just the sequencing of the TSC 1 and TSC2
and Athena was quoting around a 70-75% detection rate
- With the addition of the deletion of the TSC1 and TSC2 gene the rate raised to about 85%
- Some labs are using Next Generation Sequencing which is more likely to pick up the low level
Maoism
- Exactly how much it will increase the detection rate is not known yet
- Jennifer is working with doctors in Boston to figure out if Next Generation will be a helpful tool
and how much it will increase the detection rate
- When doing a genetic test you kind find true mutation, find nothing or find variant of unknown
clinical significance (changes in the DNA, you can’t tell if it actually causes a problem with the
protein function and don’t know if it causes TSC)
The tools are getting better and geneticist are figuring out more and labs
are more receptive at looking into the unknown clinical significance and testing other family
members to determine if it is relevant
Since more labs are able to test, everyone is having to step up their game
Question: Considering doing VNS therapy, how would that effect having children?
Not real sure, VNS works through electrical stimulation not through
medicine internally
Would think less likely to cause a problem than some seizure medications
Excellent question for your neurologist, they would better know how it
would affect you and the baby while pregnant
Question: What are some not so great medications to be on?
Any medications related to Valporic Acid are related to Open Nuero Tube
Defects like Spina Bifida
mTOR Inhibitor, cannot be on while pregnant. In Cincinnati clinic, if on the
drug have to be on birth control. The drug is used for transplant patients and can have some
negative side effects when something foreign comes into the body, like a baby
May have to go off certain drugs before conception and while pregnant, but
that does not mean you won’t be able to go back on the drugs once the pregnancy is done. Just
need to find an alternative during the time of the pregnancy.
Added thought unrelated to TSC:
If you are thinking of becoming pregnant every woman should be taking
folic acid, prenatal vitamins
Question: Was it said that there was an increased risk of developing LAM during pregnancy?
Not an increase in developing LAM, but there are cases if you have LAM
that the symptoms could become worse
During pregnancy there are increase surges of estrogen and hormones and
these surges in hormones can be relates to increase problems in LAM
Late in pregnancy any woman can have difficulty breathing because the
baby is pushing against the diaphragm
Can cause significant breathing issues in some patients that have TSC and
LAM
If you do not have LAM or have a mild case your risks are low.
Do recommend if a woman is interested in getting pregnant having a
assessments done prior to pregnancy such as a high resolution chest CT
Question: Cost of Genetic testing, is genetic testing covered by insurance and if you have it, how easy is
it to find in the children?
Cost varies by lab and what tests are done
Going through all the testing in the range of about $5,000
Most hospitals will also charge a fee for collecting and sending the lab out
Insurance is getting better and covering the testing, but varies
Becoming more commonly covered, when not covered appeal and say why
it is medically necessary
Appeal as many times as possible
Most hospitals and many labs will help those paying out of pocket with
different payment options and financial assistance programs
If the mutation that is causing the TSC is found then the testing for kids is
very straightforward, much cheaper (around $250.00), because only having to do one test
looking at the one mutation.
If kid has the same mutation, then the child has TSC, no way to predict the
severity of the manifestations.
If the mutation is not found, very likely the child will not have TSC
Question: Ways to cut cost on genetic testing?
Some people will wait for a year that they have a lot of other medical
procedures and have already met maximum out of pocket on insurance and do the genetic
testing then
Another helpful trick is genetic testing is usually covered if ordered while
you are in-patient (all those bills are usually lumped together and they don’t look to closely at it)
Personal experience shared as far as using the lab, how to pay for the procedures and Embryo Adoption:
Was able to purchase insurance through Athena, if insurance didn’t cover it,
Athena would refund some money. Was able to save a lot of money, ended up paying a little
under $1,000 out of pocket
Check with the lab when ordering the test and this is only an option for
those with a private insurance
Has a beautiful and healthy 4 year old boy
Egg donation is another option out there
Testing the embryos can put you into the 2nd trimester of pregnancy
Question: What do you tell a couple who comes in because they are overwhelmed about Tuberous
Sclerosis?
Make sure everyone is going in healthy and well-informed
Always recommend that someone who has TSC and has a new significant
other, they go see the genetic counselor together
The new partner needs to learn about TSC and all the different options
Couples should come in together and the decision should be made together
Most of the time it is not a decision that needs to be made over night, there
is time for a lot of soul searching.
One decision can be appropriate and right for one family and the complete
opposite can be appropriate and right for another
Never say you can’t have kids, just look at all the options and make the
decision that is right for you and your partner
No reason why people with TSC that can’t have children
Don’t believe that TSC is as life limiting as it was considered in the past. There are definitely some
people that pass away from TSC with severe manifestations, but that is more the minority.
Question: My daughter is pregnant and the labs in the United States would not do the testing, so they
sent her out of the United States. Will the insurance cover out of the US?
Insurance companies in the US will not pay for testing outside of the United
States
Always try and send the testing to the same lab that did the original test
that found the mutation in the parent, so that they can look back at that parent as the “positive
control” and make sure they are looking at the same thing.