Category Archives: Estie’s posts

BRCA testing for all Jews? BRCA testing for everyone?

news 2Co-written by PJGH genetic counselors Estie Rose and Chani Wiesman

This week was a very busy and exciting week for us at the Program for Jewish Genetic Health (PJGH)!  Late last week, the New York Times published two articles describing the findings and ramifications of published research conducted by renowned geneticists in the US and Israel. The first article describes a study done by Dr. Ephrat Levy-Lahad at Shaare Zedek hospital, who concluded that ALL Ashkenazi (Eastern European) Jewish individuals should be tested for BRCA mutations—not just those individuals with family histories of breast and/or ovarian cancers. Since about 1 in 40 Ashkenazis will carry a cancer-predisposing BRCA mutation, genetic testing was suggested for everyone at a young age.  Then, in case a mutation is present, it is better to find out at a preventable stage.

The second article quotes the scientist who discovered BRCA’s association with cancer and who partnered on the Israeli study, Dr. Mary –Claire King. Dr. King’s statements took this one step further, as she called for screening all American woman 30 or older regardless of race or ethnic background—not just Ashkenazis!

Our inboxes have been flooded and the phones have been ringing all week with inquires about these articles.  So how do we feel about these statements? If you have been listening to the news, the media made it sound like these are new ‘guidelines’ or ‘recommendations,’ but we prefer the word ‘opinions.’ These opinions come from a good place, where people want to prevent illness, but they are also somewhat controversial and may be considered by some to be extreme.

For starters, we think it is important to take a step back and spell out what’s so important about BRCA in the Jewish community.  After that, we will get to the “PJGH response” to these studies.

We have spoken about BRCA many (many, many!) times in this blog, but we never actually told you why it is related to the Jewish community (our oversight!). BRCA1 and BRCA2 mutations (mistakes in the genes) cause a significantly increased risk for breast and ovarian cancer, as well as some other cancers.  Just like there are certain mutations for other diseases that are more common in the Ashkenazi Jewish population, there are three specific mutations in the BRCA genes that are more commonly found in the Ashkenazi Jewish population. Numerous studies have found that between 1 in 40 and 1 in 100 Ashkenazi Jews will carry one of those three BRCA mutations and are therefore likely at an increased risk for cancer. If someone is Ashkenazi Jewish and has a BRCA mutation, the vast majority of the time, it is one of those three mutations. Furthermore, that 1 in 40 – 1 in 100 carrier frequency holds true regardless of personal or family history of cancer. So if you take any random group of 100 Ashkenazi Jews, 1 or 2 of them is likely to carry a BRCA mutation, even if he/she doesn’t have a personal or family history of cancer.

This is a big deal, and it’s a huge community issue.

So what is our current response?

Philip’s Dad, an Inspiration

Last week, my neighbor invited me over to meet his friend, Philip, and Philip’s dad.  Philip is a 26 year old man who has familial dysautonomia (FD). FD is a genetic disease that affects the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Many individuals with FD have learning disabilities and many are wheelchair-bound. FD is one of the most common genetic conditions in the Ashkenazi Jewish population, with a carrier frequency of about 1 in 30. Today, Ashkenazi Jews around the world are routinely screened for mutations in the FD gene–among many other diseases–through genetics clinics and private physicians’ offices (click here for screening resources offered by our Program for Jewish Genetic Health). Without the ability to identify and counsel carriers, the disease’s incidence among Ashkenazi babies would be 1 in 3,600!

Philip and his father greeted me with smiles and were eager to talk with me about one of Philip’s fascinations and expertises, the Jewish calendar. Since I am not too familiar with the nuances of the calendar and lunar holidays, we ended up reminiscing about popular Nickelodeon game shows from the 1990s (which was a lot of fun!). Philip’s father stuck around for this conversation. I was surprised since he could have taken a much-needed break to schmooze with the adults in the house. I had a great time talking to Philip—but I also spent a lot of time watching his father.

I thought I would share a few things I learned from Philip’s father, as well as from other parents of kids with genetic diseases and other special needs. These may seem obvious, but I find these to be very helpful in my own day-to-day experiences:

1)      If you try hard enough, you can become a more patient person. Even though it was difficult for Philip to tell long stories, his father would allow him to go at his own pace instead of interjecting.This is definitely the hardest lesson for me to incorporate into my life!

2)      Try to focus on what is, not what is not. When I first saw Philip, I saw a man with difficulties and disabilities, but I noticed that his dad simply viewed him as a son. Maybe I need to change how I perceive things.

3)      Try to turn your difficult situations into something positive for others.  Philip’s dad runs a local fundraiser for FD awareness every year in the community and runs marathons to support finding cures this condition!  And many of the support organizations out there were founded by parents of affected children who felt the need to help other parents who were going through the same experience.

4) Remember to laugh sometimes. I can not count how many times Philip and his dad joked around and laughed about silly things. I sensed that they both try not to focus on the obvious medical issues, but to look at the positive and fun things about life.

Everyone copes with difficulties in different ways, and what I saw from Philip’s dad in that 1 hour does not necessarily reflect how he always behaves. Also, there is no one “right way” when it comes to dealing with individuals with special needs. But from that one 1 hour, I was inspired.

Here are some good resources if you or someone you know would like a place to turn to:

Chai Lifeline, offering a number of services for Jewish children with life threatening illness

Jewish Genetic Disease Consortium, an organization of many smaller, more disease-specific, groups

Ramah Special Needs Programs, providing a range of camping experiences for children with special needs

Yachad, The National Jewish Council for Disabilities, dedicated to addressing the needs of all Jewish individuals with disabilities and ensuring their inclusion in every aspect of Jewish life

The Friendship Circle,  a Jewish organization for children with special needs, with over 79 locations worldwide

“Far from the Tree”, a book by Andrew Solomon telling stories of parents who not only learn to deal with their exceptional children, but also find profound meaning in doing so

Blogger’s note: I wrote this blog about 2 months ago, but never ended up posting it. Philip passed away last week, one week after his 27th birthday. Philip was an inspiration to me and our community.  May God comfort his family , together with all the mourners of Zion and Jerusalem.

The “Other” Genetic Test

Fragile-X-infographic-400-square-300x300When people inquire about how many diseases are on our Ashkenazi panel, we tell them that we currently offer screening for 18 conditions that are distinctly Ashkenazi , plus another two that are common in all populations. I have already blogged about spinal muscular atrophy, the first of those “extras”.  Today I want to review why screening for the other one, fragile X syndrome, is more complex.

Fragile X syndrome is the most common inherited form of mental retardation in boys. Affected individuals demonstrate varying degrees of intellectual and behavioral disability, sensory disorders, connective tissue problems, and physical features. About 1 in 250 women are carriers of fragile X syndrome.

When we offer fragile X screening in our clinic, we find that some patients decline. This is because fragile X carrier screening is not the same as screening for the other 19 autosomal recessive conditions. Why?

Firstly, fragile X syndrome is not recessive; it is X-linked. In the context of pre-conception screening for the next generation, only females are screened for fragile X syndrome.  If you are a carrier of an X- linked disease, you are at risk to have an affected child, regardless of your partner’s results.  Therefore, finding out that you a carrier of an X- linked disease may have a more significant impact than finding out you are a carrier of a recessive disease.

Secondly, fragile X carriers may have certain health issues. While we usually tell our patients that being a carrier has no impact on your health, this may not be true of fragile X carriers. Female premutation carriers have a 20-30% risk of developing “primary ovarian insufficiency.” This condition may lead to infertility and/or early menopause.  Male premutation carriers have a 30-40% risk for Fragile X Associated Tremor/Ataxia syndrome (FXTAS), which is often compared to Parkinson’s disease. Female fragile X carriers can develop FXTAS as well (~8% risk), however it is more common in males. So while carriers will not develop fragile X syndrome, they may at risk to develop other medical conditions. Some people want to learn more about their own health risks, while others come in to learn about their offspring only.

Finally, fragile X screening results may not be as simple as “carrier” or “non-carrier”.  I am not going to go into a detailed lesson about the fragile X mutation in this blog, but the take home message is that one may be identified as an “intermediate carrier,” which is basically a pre-carrier. This person is not a carrier, so her child will most likely not be affected with fragile X. But the mutation may change over time, causing generations down the line to become true carriers ( what we call “premutation carriers”). Some patients are confused as how to proceed with prenatal or preconception genetic testing when they learn they are intermediate carriers.

So you can see why fragile X screening is not so simple. Currently, the American College of Medical Genetics and Genomics only recommends screening women for fragile X if there is a family history of it or any other form of mental retardation, or if the patient asks for it. There is no doubt that getting screened may be helpful for family planning purposes, but it may come with a price tag of more information than you had initially wanted.

To learn more about fragile X syndrome, visit the National Fragile X Foundation. They have a fantastic infographic about fragile X (part of which is shown at the top of this blog).

August is “SMA Awareness Month”

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In an attempt to express interest in my career, my husband likes to send me interesting links to news stories and videos that relate to genetics. He likes even more to send me links to his fantasy baseball players’ accomplishments. This week was his crowning achievement, as he sent me one that combined genetics and baseball. It was a video and article from ESPN.com about a 6 year old boy and his twin sister, both of whom have spinal muscular atrophy (SMA). The boy’s dream was to play for the Arizona Diamondbacks. The video is incredible and is a real tear-jerker!

If you or your partner has been pregnant in the past few years, you might have heard of SMA since your OB/GYN may have offered you genetic testing for this condition. SMA is an inherited disease of the motor nerves that causes muscle weakness and atrophy (wasting). Motor nerves arise from the spinal cord and control the muscles that are used for activities such as breathing, crawling, walking, head and neck control, and swallowing. So if the motor nerves are not working properly, these bodily functions are compromised.  In his book “Genetic Rounds,” pediatric geneticist Dr. Robert Marion (Einstein) describes SMA as “the childhood equivalent of the better-known, but also poorly understood, amyotrophic lateral sclerosis, more commonly known as Lou Gehrig’s disease…” (pgs 85-86). SMA is a rare disorder occurring in approximately 8 out of every 100,000 live births, and is the leading cause of infant death. There are four types of SMA, which range from lethal in infancy to a less severe form that develops in adulthood.

Like other Ashkenazi Jewish diseases we have talked about on this blog, SMA is inherited in an autosomal recessive pattern. So if both parents in a couple are carriers of SMA, there is a 1 in 4 chance for them to have a child who is affected.

The reason many OB/GYNs order SMA testing is because in 2008, the American College of Medical Genetics and Genomics came out with a Practice Guideline that said: “Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity.” Recent studies have shown that the carrier frequency is about 1 in 56 in the general population, and about 1 in 67 in the Ashkenazi Jewish population.

If you look at our current panel of diseases for screening our Ashkenazi patients, you will see that based on carrier frequency, SMA is actually more common than many of the other diseases on the panel. I would like to point out that even though it is more common, SMA does not fall under the category of “Ashkenazi Jewish genetic diseases.” This is because those conditions have known “founder mutations,” or genetic changes that are frequent in that specific population. SMA mutations are common in ALL populations, not just in Ashkenazi Jews. Since we often see patients who come for Ashkenazi testing before a pregnancy, we recommend that they also get screened for SMA at the same time. This is also true for the Sephardic and non-Jewish patients we see.

August is “SMA Awareness Month.” To learn more about SMA and the research initiatives to treat it, go online to the SMA Foundation website.  Personally, I am made aware of SMA every day since my neighbor is affected with type II SMA and I see her playing outside in her wheelchair all the time. But for those of you who do not know anyone who is affected, try to become aware that this condition exists. Make sure to get screened before a pregnancy or early into one, and spread the word to your child-bearing friends and family. You could really make the difference!

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