September is National Tay-Sachs Awareness Month – but for a Yale genetic counselor every day is about Tay-Sachs awareness.

By Cindy Mindell

NEW HAVEN – September is National Tay-Sachs Awareness Month, a designation unanimously ratified by Congress in 2008. The vote came four decades after the first grass-roots efforts and organizations around the country had begun to raise awareness and research funding to battle the rare but fatal inherited genetic disorder. Tay-Sachs occurs more frequently in the Ashkenazi Jewish population, where it is estimated that one in four individuals is a carrier of the genetic mutation.

The first successful screening test for Tay-Sachs was developed in the late ‘60s by Dr. Michael M. Kaback, who in 1979 was tapped to serve on the first National Institutes of Health panel to recommend prenatal testing for genetic diseases. Since then, awareness and testing options have only grown, and the frequency of the fatal Tay-Sachs disease has declined dramatically.

For Miriam Schoenfeld DiMaio, a senior genetic counselor in the Yale School of Medicine’s Department of Genetics, every day is about Tay-Sachs awareness. In daily consultations with patients seeking reproductive counseling, DiMaio offers recessive gene screening that is in part based on ethnic background. People of Middle Eastern, African, and Southeast Asian ancestry have an increased risk for certain inherited anemias. Caucasians have an increased risk for cystic fibrosis. Jews – Ashkenazi, Sephardi, and Persian – may carry other genetic disorders.

DiMaio spoke with the Ledger about the world of genetic disorders – Tay-Sachs and others – and how screening can help couples make sound reproductive choices.

Jewish Ledger (JL): On one foot, explain how Jewish genetic disorders came about.

MD: For the Ashkenazi disorders, what probably happened is that one or two individuals emigrated from the Middle East to Europe 2,000 years ago, had a genetic mutation for one or more of these disorders, and had a lot of kids. And then, since the Jews tend to marry amongst themselves, the mutations stayed in this population group and were perpetuated. That’s why they are more unique to the Ashkenazi or Persian Jews. There are disorders that are more common among Sephardic Jews, and those diseases are also seen in people from countries where Sephardic Jews live, but who are not Sephardic.

The Persian Jews are a unique population: they were genetically isolated for at least 1,000 years – maybe 2,000 years – and we didn’t know much about their genetics until they left Iran and came here, where they were very well-studied by geneticists, especially Dr. Michael Kaback in Los Angeles, who was the spearhead for Tay-Sachs testing 30 or 40 years ago. He really has been a giant in the field of Jewish genetic disease screening. He started to characterize the recessive gene mutations in the Persian Jewish population, and so this population can avail themselves of the testing.

JL: You have worked as a genetic counselor for more than 30 years. How would you describe the current state of genetic screening?

MD: Genetic technology has exploded so we are able to do recessive gene carrier testing for many disorders, including a bunch of disorders that are more common among Eastern European Jews. There are also genetic disorders that are more common among the Persian Jews, the Jews from Iran, who immigrated to the United States after the fall of the shah, and there’s also carrier testing available for this group of disorders. The testing is very good; it’s very sensitive, so it tends to find most carriers of these conditions in these population groups.

These tests can be done as stand-alone tests – looking for disorders that are more common among these populations – or you can do them as part of panels that include testing for other recessive conditions that are not specific to the Jewish population. The whole screening paradigm is changing because there are now commercial labs that are testing for 100 or more recessive disorders, which include the Ashkenazi disorders.

Although the Ashkenazim have 15 or 16 disorders that are more common than in other population groups, for most of these disorders the risks in absolute terms are still quite small, so it’s not something to be alarmed about in a major way. Since there is very good carrier testing available, couples have the option of learning ahead of time whether they’re at high risk and they can take advantage of reproductive options to help them avoid the birth of a baby that has a very serious disease.

[Editor’s note: A carrier is an individual who does not develop the disease, but can pass the gene with a mutation to his/her children.]

JL: In terms of genetic screening, what do you recommend to couples who want to start a family?

MD: If you’re thinking of having children, it’s better to get tested before pregnancy than during pregnancy. It’s okay to get tested during pregnancy but you’ve got more options if you do it before. If it’s done prior and the couple is found to be at high risk for a very serious disorder, they could take advantage of options. For example: in-vitro fertilization, then testing embryos conceived outside the womb for the genetic mutations, and then only transferring embryos that are predicted to be unaffected back into the womb. If there are many embryos that are available for transfer – we don’t want “octo-moms” anymore – we recommend that embryos be frozen for future use. That’s done safely and successfully.

JL: Do genetic diseases like Tay-Sachs affect only Jewish populations?

MD: That’s a common misconception. People say, “I’m not Jewish so I don’t have to worry about Tay-Sachs disease” or some other disorder. They do have a risk; it’s just a much smaller risk than is present among someone who’s Jewish. Many people have buried Jewish ancestry. The Holocaust resulted in a couple of things happening: Jewish children were adopted or taken by Christian families and never told of their identity. People converted pre- and post-Holocaust, a la Madeline Albright, where people never knew until they were adults that they were Jewish. That’s another reason that we see Jewish genetic disorders occurring in people who aren’t Jewish because they actually do have buried Jewish ancestry. So, when you’re thinking about testing, just because someone says they’re not Jewish doesn’t mean that they’re not at risk; they’re at lower risk. Clearly, someone who’s from Iceland has a lower risk than someone who’s from Czechoslovakia. But we all have a risk for having the Tay-Sachs gene mutation, for example, regardless of our ancestral background.

JL: With so many known genetic diseases, why does Tay-Sachs get its own awareness month?

MD: I think that Tay-Sachs is the paradigm, the recognizable disorder that people know about that’s more common among Ashkenazi Jews. To put that into perspective: an Ashkenazi Jewish couple that has not been tested has a one in 3,600 chance of having a baby with Tay-Sachs disease. If you’re Ashkenazi-Jewish, your chance of being a carrier is one in 30. Tay-Sachs is the example but there are other diseases that are equally severe, that have very serious consequences for a child, that have lower gene frequencies – and so, a lower incidence – that are more common. So, when we talk to couples about carrier testing, we don’t just restrict it to Tay-Sachs disease; we talk about all the disorders that are more common.

JL: Has the Tay-Sachs awareness campaign affected the incidence of testing?

MD: It has dramatically reduced the incidence of Tay-Sachs in the United States among Ashkenazi Jews. In fact, in this country, more babies with Tay-Sachs disease are born to non-Jews than to Jews. Jews are very amenable to screening and medical intervention, so they take advantage of it. Since 1983, the Orthodox Jewish community has had access to the Dor Yeshorim Committee for Prevention of Jewish Genetic Diseases. Before you get set up with your prospective mate, you are tested for these Jewish genetic disorders and then the rabbi tells you who you can date and who you can’t date. Jews are a well-educated population and are interested in taking advantage of medical advances, and so they participate in studies and research and it has benefited them in this way.

For more information: Jewish Genetic Disease Consortium, jewishgeneticdiseases.org, Miriam.demaio@yale.edu.

The Cure Tay-Sachs Foundation, a non-profit organization founded in 2007 and affiliated with National Tay-Sachs and Allied Diseases, raises funds for research to find treatments and a cure: curetay-sachs.org.