Understanding Jewish Genetic Diseases

Within our cells are the instructions for how our bodies work and how we look. The instructions are called genes, which are composed of DNA. We get one half of our genes from our mother and the other half comes from our father; therefore, we have two copies of every gene. There are thousands of genes within the human body and every one of us carries some genes that may not function properly.

There are several ways that genetic disorders are inherited. One, which is how most of the Jewish genetic diseases are inherited, is called autosomal recessive inheritance. In these genetic diseases, both copies of a pair of genes are altered, and this causes the person to have the genetic mutation. A person with one gene change is called a carrier.

Autosomal recessive conditions affect both males and females; the parents of these individuals are usually unaffected, and there is often no family history of these conditions. When a couple has one child with an autosomal recessive condition, there is a 25% chance during each future pregnancy of having another affected child.

Everyone, regardless of ethnicity, religion or race is at risk for genetic disorders. It is thought that all of us carry at least six to eight gene changes which could result in genetic disease. It has been well established that certain genetic conditions are seen more commonly in certain ethnic groups. For example, sickle cell anemia is seen more frequently in individuals of African descent, individuals of Mediterranean descent are at risk for thalassemia (a blood disease), and Caucasian individuals of European descent are at risk for cystic fibrosis.

Ashkenazi (Eastern European) and Sephardic (Spanish/Mediterranean) Jews are no exception. Several conditions have been identified in Ashkenazi Jews and there are a few reasons why this is so. First, Jews migrated from the Middle East to Eastern Europe due to the Diaspora. Second, if this group of immigrants had one ancestor who had a gene change, it would be passed on to many generations.

Lastly, given Jews tended to marry other Jews which further increased the chances that a gene mutation change would be found in the group. As Jews further migrated to the United States and other areas of the world, these genes have remained within the Ashkenazim. Sephardim are at risk for different conditions compared to the Ashkenazim.

Detection rate is the percentage used when describing the chance that a given test will identify the condition you are actually testing for. For example, the detection rate for testing for Canavan disease is 98%.

That means that if an individual of Ashkenazi Jewish descent chooses to have screening for Canavan disease and this person is truly a carrier for Canavan disease, 98 percent of the time genetic testing will identify a gene mutation. This also means that 2 percent of the time, a carrier will test negative for the disease and a gene mutation change will not be detected, even if it is there.

Therefore, this genetic testing is not 100 percent perfect. If you test negative for any of the conditions, you still have a small risk of being a carrier. By testing negative, you are greatly reducing your chances of being a carrier of a gene and for many people this information is very helpful. Most of the tests for the Jewish genetic diseases have a detection rate of 95% or better.

This list is not all-inclusive and may change over time. Options for testing are lab-dependent.

Please contact your primary care physician, your obstetrician, gynecologist, or genetics professional for additional information regarding testing for these conditions

Bloom Syndrome
Growth delay, which can start prenatally, is the first sign of concern in most affected children. Certain physical features that are typical Bloom syndrome symptoms include a small jaw, long limbs and large hands and feet.

Another common finding is a weakened immune system, as well as sensitivity to light. For the majority of affected individuals, intelligence is normal. People with Bloom syndrome have a significantly increased chance to develop cancers such as leukemia and lymphoma, over the general population risk. Therefore, this can lead to premature death in the 20s or 30s.
Bloom's Syndrome Foundation
http://www.bloomssyndrome.org/

Canavan Disease
Infants with Canavan disease may appear normal in early life; however, developmental delay and lack of head control may be noticed at 3-6 months. Affected children can learn how to smile, laugh and visually track objects although, they may not be able to learn how to sit, walk or talk.

Over time, seizures may develop. There is variable life expectancy, with some individuals surviving only the first few years of life, while others live into adolescence.
Canavan Research Foundation
http://www.canavan.org/
Phone 203-746-2436

Cystic Fibrosis
Cystic fibrosis is a disease which affects the respiratory tract, pancreas, intestine, liver, male genital tract, and the sweat glands. Lung disease is the major cause of illness and death in affected individuals. Abnormal function of the pancreas leads to poor weight gain.

Affected males are usually infertile due to structural abnormalities of the reproductive tract. The average lifespan for individuals affected with this condition is approximately 40 years.
Cystic Fibrosis Foundation
http://www.cff.org/
Phone: 301-951-4422 or 800-FIGHTCF(344-4823)

Familial Dysautonomia
This condition, also called Riley-Day syndrome, affects the part of the nervous system which is responsible for the body’s response to stress. Individuals with this disease may have altered sensitivity responses to pain and temperature. They can also have gastrointestinal problems, excessive sweating and vomiting episodes.

Affected infants may have developmental delay, especially due to decreased muscle tone. In older individuals, there may be difficulty with balance. Intelligence is usually normal. Approximately half of affected individuals can live up to 30 years.
Dysautonomia Foundation,Inc.
http://www.familialdysautonomia.org/
Phone: 212-279-1066

Fanconi Anemia, Type C
This condition is usually diagnosed before 12 years. Easy bruising and frequent nose bleeds can be the first sign of concern, as well as short height. Physical findings may include hand or arm abnormalities (specifically with the thumbs), kidney problems, congenital heart defects, or gastrointestinal difficulties.

Affected people may be mentally retarded or have learning disabilities. Anemia can lead to bone marrow failure and many people with this disease develop a form of leukemia at a young age. They are also at an increased risk to develop other types of cancers. Individuals with this disease usually live into their early 30s.
Fanconi Anemia Research Fund,Inc.
http://www.fanconi.org/
Family Support Toll-Free Line (in United States):800-828-4891

Gaucher Disease, Type I
Affected individuals may experience periodic deep bone pain (‘bone crises’), as well as mild to severe abnormalities of the bones on x-ray. An enlarged spleen can lead to abdominal pain. Many people with this disease develop anemia due to the abnormalities of the spleen and bone marrow.

Lung disease (pulmonary hypertension) can be seen is some affected individuals. Gaucher disease symptoms can begin during childhood or not until later in life. Lifespan is not shortened and enzyme replacement therapy is available.
National Gaucher Foundation
http://www.gaucherdisease.org/
Phone: 800-925-8885

Mucolipidosis, Type IV
Delays in development can be seen by one year of age. Most children with this disease will never walk independently and have poor use of their hands. Language development is weak, with most affected individuals using only a few words.

Developmental abnormalities of the brain can be noted using MRI (magnetic resonance imaging) and vision gets worse over time due to abnormalities of the retina. Affected individuals can survive into adulthood.
Mucolipidosis IV Foundation
http://www.ml4.org/
Phone: 718-434-5067

Niemann-Pick Disease, Type A & B
Type A is characterized by severe neurologic disease, which is usually seen in the first few months of life. Some Niemann-Pick disease symptoms may include an enlarged abdomen and ongoing loss of developmental skills. Feeding difficulties may also be observed. There is currently no treatment, and death usually occurs by 18 months.

Type B typically does not have any neurologic involvement. An enlarged spleen and/or liver may be seen in ‘pre-teen’ years. Due to lung damage, extra oxygen may be required. Life expectancy is longer than for Type A, however prognosis is variable.
National Niemann-Pick Disease Foundation
http://www.nnpdf.org/
Toll Free: 877-CURE-NPC (877-287-3672)

Tay-Sachs Disease
In the infantile form of Tay-Sachs, affected babies can appear to be completely normal at birth and then develop symptoms between 3-6 months of age, such as loss of motor skills or declining weakness. They may also demonstrate an ‘exaggerated’ reaction to loud noises.Seizures and blindness can develop and death occurs before the age of 4 years for the majority of affected children. There is no Tay-Sachs disease treatment.

National Tay-Sachs and Allied Diseases Association, Inc.
http://www.ntsad.org/
Phone: 800-906-8723

Please contact your primary care physician, your obstetrician, gynecologist, or genetics professional for additional information regarding testing for these conditions.

Cooley’s Anemia Foundation
https://www.thalassemia.org/
Phone: 800-522-7222

National Human Genome Research Institute—Learning about Familial Mediterranean Fever
http://www.genome.gov/12510679

An Introduction to G6PD deficiency
http://webprojects.oit.ncsu.edu/project/bio183de/Black/enzymes/enzymes_news/G6PDHOMEPAGE.html

Now is the time! Whether you are single, getting married, currently pregnant or have a family history of a Jewish genetic disease, carrier genetic testing is available to you. Finding out if you are a carrier of a gene will provide you with information regarding your risk to have a child affected with a recessive disease.

This information may also help you make decisions about undergoing either preconception or prenatal testing during a current or future pregnancy.

The first step in screening is to meet with a professional who can answer your questions. You may wish to speak with your Rabbi, your primary care physician, your obstetrician or gynecologist, or with a medical geneticist.

Medical geneticists or genetic counselors are both genetic professionals that can guide you through the process of genetic testing. Many issues should be considered before genetic testing and these professionals can help you sort through your thoughts.

If you decide to have genetic testing, it is done by drawing a blood sample. Because this is medical testing, it must be ordered through a physician. You may choose to have genetic testing for one, some or all of the conditions listed on this site. For more information on genetic disorders, please refer to the Which Diseases are Ashkenazim at Risk For question above.

The results generally take one to two weeks and are reported back to you by the ordering physician.

Your insurance company may cover some or all of the screening tests. It is common for insurance to cover the cost of genetic testing for certain genetic diseases, as they are considered “standard ofcare.”

It is best to check with your individual insurance provider for coverage. Some people may be concerned about insurance discrimination; however, more and more, state and federal laws are being passed to ban various types of insurance discrimination.

Although the genetic conditions discussed on this site (please refer to Which Diseases are Ashkenazim at Risk For), are more commonly found in people of Ashkenazi Jewish descent, these conditions can be seen in people from other ethnic groups.

Sometimes, the chance for carrying the disease is lower for non-Jews. For example, someone of Ashkenazi Jewish descent has a 1 in 30 chance of being a carrier of Tay-Sachs disease, but someone who is non-Jewish has a 1 in 300 chance of being a carrier of the same genetic condition.

So, the chance that a couple of mixed ancestry would have a child with one of these conditions we describe in this packet is lower, but not zero, than for two Jewish individuals.

If you are concerned about the chance for your chances of having a child with one of these genetic disorders and you are interested in screening for them, it is best to begin genetic testing the member of the couple who is Jewish. Screening is more reliable for the person who has the higher risk.

If testing shows that you are a carrier of a recessive disease, the next step is to determine your partner’s carrier status. If your partner has a normal test result, this greatly decreases the chances that he/she is a carrier; however testing cannot completely rule out carrier status.Therefore, this also greatly decreases the chances that you, as a couple, may have an affected child.

When both members are carriers of the same recessive disease there is a 25% chance of having a child who is affected.Finding out your carrier status prior to pregnancy may allow for preimplantation genetic diagnosis (PGD). PGD involves in vitro fertilization, and is the process of performing genetic testing of known gene changes prior to implanting an embryo. This test can identify the embryos that have inherited both of the “changed genes”, and therefore can ensure that implanted embryos are not affected with the genetic disease in question. For couples who choose not to do PGD or for couples who have carrier testing during pregnancy, prenatal diagnosis may be available. Chorionic villus sampling (CVS) is available between 10-12 weeks of pregnancy and amniocentesis is available between approximately 16-20 weeks of pregnancy.

Both CVS and amniocentesis are procedures in which there is a small risk for complications which may lead to miscarriage. You will definitely want to discuss your options with a medical geneticist and your physician to better understand the risks and benefits of your choices.Some couples choose not to do PGD or prenatal testing, even if they are both carriers. If there is any suspicion that a baby is affected at birth or at some other point in development, genetic testing can be performed at that time.