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Interview with Ellen Simpson: Prenatal Tests and Carrier Screening for Genetic Conditions

Audio Interview

Hear Ellen Simpson, a genetic counselor at the UCSF Prenatal Diagnostic Center, discuss the latest in screening, testing and counseling. Genetic testing can help patients learn if they're carriers of genetic conditions and what chances they have of passing on the disease.

Interview Transcript

Introduction

Andrew Schorr:

While most women give birth to healthy babies, it's estimated that about 3 percent give birth to a baby that has a birth defect that is clinically significant, and in many cases these birth defects are caused by a genetic or chromosomal disorder. You'll hear about screening for potential parents to see if there's the potential for genetic defects in that baby. It's coming up next on Patient Power.

Hello and welcome to Patient Power. I'm Andrew Schorr. This program is sponsored by UCSF Medical Center, one of our leading medical and research centers. You're going to hear about prenatal screening and carrier screening for folks who are going to have a baby or who would like to have a baby and worry that there could be a genetic defect.

UCSF does a lot of research in this area to help us better understand it and here to discuss it in depth is Ellen Simpson. She is a genetic counselor at UCSF in the Prenatal Diagnostic Center. Ellen, thank you so much for joining us. I'm very interested because I'm of Ashkenazi Jewish descent. Now Ashkenazi Jews from Eastern Europe, we have kind of a higher incidence of some of these genetic abnormalities that could cause a birth defect, don't we?

Ellen Simpson:

Yes that is true. Each of us carries changes in about eight different genes which could potentially lead to a problem in offspring, but certain groups have been studied a little bit more, and we have a lot more to offer those people in terms of specific information about which genes are likely to be affected, and that's the case for the Ashkenazi Jewish population.

Andrew Schorr:

What we're trying to understand, give the benefit to potential parents is, know if you're a carrier and you individually and how that matches up with the person who would be the other parent and understand what the risks are for certain conditions. What are some of these conditions?

Ellen Simpson:

The most common in the Ashkenazi Jewish population is Tay-Sachs disease, and many people are familiar with that. There was very widespread acceptance of screening in the Jewish community. There was also a very good ability to detect whether individuals were carriers, and that's been going on for a number of years. There's also prenatal diagnosis available in situations in which both members of the couple are carriers.

Another disorder for which screening is commonly available in the Ashkenazi Jewish population is Canavan disease, for which there's a very good detection of carriers.

One that's been more recently added is Familial Dysautonomia, and the detection is very good for that. It's not as common as the other disorders, but the detection rate is very high and the potential morbidity is very high. It's a severe disorder.

Cystic fibrosis carrier testing is also commonly offered in the Ashkenazi Jewish population. It is not more common in that population than in the general Northern European population, but the ability to detect carriers is very high.

Benefits of Carrier Screening

Andrew Schorr:

All right, and I know it can be tragic when someone has a baby that develops one of these conditions. I have friends where their third child was born with Tay-Sachs. The parents had no idea that they were carriers and that they were at risk, and that child lived to be about three. Of course they're aware of the diagnosis very early on in the child's life and knew that that would be the inevitable end. It was very tragic.

So how can carrier screening help couples head that off?

Ellen Simpson:

We can meet with people before they're pregnant or during the pregnancy, and we can even work with potential partners and sperm banks to make sure the individuals are offered the option of having carrier detection for the most common disorders. There are a number of other disorders in the Ashkenazi Jewish population for which carrier testing is also available. We can explain to them how the testing is done, make it available, get them the results, and then when we have the results on both parents calculate the estimated risk for a pregnancy between those two individuals to be affected.

Andrew Schorr:

All right, now the testing for these conditions we've mentioned, is it typically a blood test?

Ellen Simpson:

Yes it is.

Andrew Schorr:

So you come back with a result. Now is it necessarily true that even if people were carriers that each child would have that condition?

Ellen Simpson:

That's an excellent question. No, the greatest likelihood is that the children would not be affected. If both members of a couple are carriers the chance for each pregnancy, which is an independent event of course, or for each member of a non-identical twin pair is one in four.

Andrew Schorr:

As I said with my friends, they had two healthy children before they had a third child that was diagnosed with Tay-Sachs, but of course the parents as we found out were carriers all along.

We're talking about Ashkenazi Jews but there are other conditions of course that affect a broader population where maybe there's a family history involved. So tell us about some mental health conditions. Isn't one, is it Fragile X? Is that one of them?

Ellen Simpson:

That's correct. Fragile X is the most common form of inherited mental retardation. It's not the most common cause, but it is the most common inherited cause of mental retardation. This is a disorder in which only one member of the couple needs to be a carrier in order for there to be an increased risk for the offspring; however, we are very good at detecting carriers.

Andrew Schorr:

Does that mean if somebody is aware of their family history that as they're considering becoming pregnant that carrier screening might be a wise thing to do?

Ellen Simpson:

Absolutely. Fragile X carrier testing should be offered to individuals who have a first-degree relative with mental retardation. In addition, because it's on the X chromosome and largely affects males we offer it to anyone with a family history which is consistent with X-linked inheritance of mental retardation.

Andrew Schorr:

One other one I read about is spinal muscular atrophy?

Ellen Simpson:

That's correct. Spinal Muscular Atrophy (SMA) is not associated with mental retardation or psychiatric disorders, but it is associated with significant physical disabilities in most cases. The availability of testing is relatively recent, and it is being offered not to any specific ethnic group; there isn't any ethnic predilection in this disorder.

SMA has a similar type of inheritance as the disorders we discussed in the Ashkenazi Jewish population where both members of a couple would need to be carriers in order for the child to have a one in four chance of being affected.

Pre and Post-Pregnancy Diagnostic Options

Andrew Schorr:

So if a test comes back positive, there's counseling for the couple and then some decision making to do. Help us understand some of the options. For instance, if you decide that you want to have babies, are there sort of other chances down the line to understand that early embryo where does it stand with actually having one of these conditions?

Ellen Simpson:

The options begin really before a person gets pregnant. Some people want to start with in vitro fertilization and diagnosis before the embryo is even implanted, and in that case for all of the above discussed disorders it is possible to determine whether an embryo has two copies of the affected gene, one from each parent and would thus be affected, one copy and in that case would be a carrier like the perfectly normal healthy parents, or no copies and would not even be a carrier.

For people who don't want to do preimplantation genetic diagnosis (PGD) there is early pregnancy diagnosis by chorionic villus sampling (CVS), which involves taking a small part of the placenta. The placenta is made by both the mother and the embryo early in pregnancy. The embryo divides and part goes to make the fetal body and part goes to make the fetal part of the placenta, and it's that fetal part of the placenta which is sampled in CVS. Those cells can be used for the same type of testing.

Alternatively, an amniocentesis can be done between 16 and 20 weeks of gestation in which a little bit of fluid is taken from around the baby, and in there are skin, lung, and bladder cells, which are the tissues of the fetus which are in contact with the amniotic fluid. Those cells are grown in the lab and again the same type of analysis is done looking for how many copies of a specific gene change are present.

Andrew Schorr:

I understand there's a test that you do at UCSF that is not at all widely done called nuchal translucency. What is that?

Ellen Simpson:

The nuchal translucency is a measurement which requires specific training and certification for the performing sonographer because it's done between 10 and 14 weeks of pregnancy when the fetus is very small. There's an area at the back of the fetal neck which is supposed to be there called the nuchal translucency (NT), and there's a range of usual values for each week of pregnancy. If the NT measures above a certain value we know that there is an increased risk for a chromosome abnormality such as Down syndrome, for a fetal cardiac defect, or for one of a number of individually rare genetic syndromes.

Andrew Schorr:

All right, let's walk through an example. Let's take the couple that is Ashkenazi Jewish and they want to have a baby. They come to you for carrier screening and let's say whether it's for Tay-Sachs or one of the others, it's positive. So there's a possibility, as you said one in four, with each pregnancy that the baby could have one of these sometimes just terrible and early life-ending conditions.

What happens next? What are the options you describe? And then where do some of these other testings if they're going through with the pregnancy at what time in the pregnancy do they come into play?

Ellen Simpson:

Preimplantation genetic diagnosis would be done at the time of IVF, so that's done even before a pregnancy is established the embryos are screened. That would involve working with a prenatal center, which has an association with a fertility center, and there are a number of excellent fertility centers which do this type of embryo screening in concert with a genetics division.

We would help couples have prenatal diagnosis as early as they wish. We would discuss with them the options, including CVS or amniocentesis. The risk associated with CVS or amniocentesis is the same, so it's really a personal choice as to whether they want to have the testing done at 10 to 14 weeks by CVS or at 16 to 20 by amniocentesis. So we would help them set up which kind of testing they wanted and where the testing would be sent for the mutation analysis.

Andrew Schorr:

Ellen, so you go through this testing. Now you mentioned nuchal fold translucency. Would that come into play for this couple concerned about Tay-Sachs or one of the other Ashkenazi Jewish conditions?

Ellen Simpson:

No. That is more a general part of prenatal care now. It is more an indicator of a risk for a chromosome abnormality, and that can be sort of confusing for people because we're talking about genes, and people say well genes are on chromosomes, what's the difference?

What we call a chromosome abnormality is a case in which an individual has an extra or a missing entire chromosome, for example in Down syndrome individuals instead of having two copies of chromosome 21, one from each parent, have three copies of chromosome 21. In other cases of chromosome abnormality an individual may have an extra or missing portion of a chromosome (duplication or deletion).

Chromosome abnormalities do not typically run in families. So the nuchal translucency is more a general part of screening for every pregnancy. It is now widely accepted, although it is as you pointed out not always widely available.

Andrew Schorr:

So at your center at UCSF you have a whole variety, maybe certainly a wider range of tests and some that are in research as well available for couples who have these concerns, and also you have the counseling to go with it.

Ellen Simpson:

That is correct, and we are very happy to be able to offer our services to anyone who is interested in obtaining them.

Andrew Schorr:

You mentioned the slight risk related to CVS or amniocentesis, and that's something parents always have to consider. Where are we now related to research on having less invasive testing where maybe those concerns would be not concerns?

Ellen Simpson:

That is an excellent question. Many people are working very hard on trying to look at fetal cells in maternal blood, and there are periods of time when we think we're very close to being able to do the mutation analysis and other types of testing on fetal cells from maternal blood, however, it just has not yet been as routinely reliable in predictive ability as the more invasive tests. That certainly is the place that everyone wants to get where it's not necessary to do an invasive test on a pregnancy.

Support for Families with a New Diagnosis

Andrew Schorr:

One thing that people may wonder about is if they come to you as a counselor, and let's say there are positive results. A pregnancy is likely to be affected by one of these conditions, or maybe a baby that is very early and there are indications that it's developing Down's syndrome. People might worry that you might not only counsel but that you would advocate a certain direction that may go against their own feelings. How does that work out so that you give them counseling but not a firm push in one direction or another?

Ellen Simpson:

I'm so glad you asked that question. All of us have worked with many families who from the beginning indicate that they will continue a pregnancy no matter what information they receive, that they simply want to know more about the baby, and they want to be prepared for what's ahead. We have wonderful support services here through our medical social workers and many resources in the community, people with whom we've worked for years and years.

We also can put families with a new diagnosis in touch with families who have been living with a child with most of the conditions with which we work who can really offer support and guidance to our families with a new diagnosis.

Andrew Schorr:

It's really about just being well educated into what is your specific situation or in the case of a baby that's already developing what is that baby's status.

Ellen Simpson:

That's correct. The genetic counseling aspect that I find very rewarding is helping people work through themselves what their decision will be because sometimes people come in for carrier testing or prenatal diagnosis, and they're not sure what they're going to do with the information but they know that they want to have it. They don't know what their final decision will be, and we are all very experienced with supporting people through that difficult time when they really don't know yet how they're going to use the information.

Populations That May Benefit from Screening

Andrew Schorr:

Ellen, just to underscore which populations should maybe pay special attention to this; Ashkenazi Eastern-European Jewish descent like me, we've been inbreeding for thousands of years, so we have a higher risk of some of these conditions, potentially fatal for young babies, so we would do well to be screened; and then you mentioned about the other population where there are, like fragile X, there are certain mental health condition risks that have been demonstrated in the family.

Ellen Simpson:

That's correct, and one thing that's starting to happen now is that many obstetricians are doing cystic fibrosis carrier screening on their patients so we're getting a lot of people who have already been found to be carriers and haven't yet had the counseling in terms of what that means for the pregnancy or for their partner.

Cystic fibrosis is a little more common in the Northern European population in general and the ability to detect a carrier is better in that population, but it occurs in every different ethnic group, so that's an area where we're seeing a lot of people who haven't been selected on the basis of ethnicity.

Another group of disorders we didn't discuss previously is the hemoglobinopathies. Hemoglobin is the protein that binds to iron and carries oxygen through our blood. This is a protein with lots of different changes, some of which are more common in the Mediterranean and through the Middle East; Africa, Asia, Southeast Asia, there are different changes that are more common in different populations. We often see people who have had a preliminary test through their regular obstetrician which indicated an increased risk for a hemoglobinopathy, and we follow up on those families also.

Andrew Schorr:

So the old saying is "knowledge is power" and I see this really applies to carrier screening and the other testing in helping families really be aware of the risk of some of these conditions or is it in fact developing in a fetus.

Ellen Simpson:

And it's important for patients to realize that they do have the power, and our job is to guide and advise but that the decisions are made by the patient and the couple, and our role is to be as supportive and as informative as we possibly can be for them at every step in that process.

Andrew Schorr:

Ellen Simpson, genetic counselor at the Prenatal Diagnostic Center at UCSF Medical Center in San Francisco, good luck with all the research and giving us even more information, and thanks for all you do for families.

Ellen Simpson:

Thank you. It's truly my pleasure.

Andrew Schorr:

This is what we do on Patient Power is connect you with leading experts, and there are certainly many at UCSF Medical Center. This is such an important area not just from my population, Ashkenazi Jews, but really so many families as they consider having a child.

Recorded July 2009

 

Reviewed by health care specialists at UCSF Medical Center.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.