The term Ashkenazi refers to individuals descended from the medieval Jewish communities of the Rhineland in the west of Germany. Many Ashkenazi Jews (AJ) migrated to other parts of Europe, with the majority migrating eastward.
The conditions for which carrier screening is offered are more common in individuals of Ashkenazi Jewish descent than other ethnic groups because of specific mutations that occurred in "founders" of the population. Because Jewish individuals historically married within their own ethnic group, these mutations increased in frequency over generations.
What are the Ashkenazi Jewish genetic disorders?
Screening is available for eleven genetic disorders. Carrier frequency is different for each condition — the overall chance of being a carrier for at least one of these diseases is 1 in 4 to 1 in 5 for someone of AJ descent.
Of these conditions, Canavan disease and Tay-Sachs disease are among the most common and severe. Both are progressive conditions with no effective treatment options at this time. Canavan disease and Tay Sachs disease are usually fatal in childhood.
Cystic fibrosis (CF) is also common in individuals of Caucasian ancestry. All of these disorders are also found in non-Jewish individuals, but with lower incidence (with the exception of CF).
Clinically Available Screening for Individuals of Ashkenazi Jewish Descent*
Condition | Disease Incidence | Carrier Frequency | Carrier Detection Rate |
Tay Sachs disease | 1/3,000 | 1/30 | 98% |
Canavan disease | 1/6,400 | 1/40 | 98% |
Cystic Fibrosis | 1/3,000 | 1/29 | 97% |
Familial Dysautonomia | 1/3,600 | 1/32 | 99% |
Bloom syndrome | 1/40,000 | 1/100 | 97% |
Fanconi Anemia group C | 1/32,000 | 1/89 | 99% |
Gaucher disease | 1/900 | 1/15 | 95% |
Mucolipidosis type IV | 1/62,500 | 1/127 | 95% |
Niemann-Pick disease type A | 1/32,000 | 1/90 | 95% |
Glycogen Storage 1a | 1/20,000 | 1/71 | 99% |
Maple syrup urine disease | 1/26,000 | 1/81 | 99% |
* Disease incidence, carrier frequency and detection rates among individuals who are not of Ashkenazi Jewish descent are available by contacting a genetic counselor at the UCSF Prenatal Diagnostic Center.
Who should consider carrier screening?
Based on recommendations from the American College of Medical Genetics, the American College of Obstetrics and Gynecology, and other groups, you should consider carrier screening if you, your partner, or both are of AJ descent.
Carrier screening is typically performed stepwise by screening the individual with AJ ancestry. It is recommended to start with testing of the Ashkenazi Jewish partner and to test the non-Jewish member of the couple only if the Jewish partner is a carrier of any of the diseases. Carrier screening is less sensitive and less informative in non-Jewish individuals.
When both partners are AJ, carrier screening can be done on either partner. Carrier screening can be done simultaneously for both parents, if time is a constraint.
When should testing be done?
The ideal time to undergo carrier screening is before pregnancy, but carrier screening can be done during pregnancy. If you are already pregnant, we recommend having carrier screening as early in the pregnancy as possible so the results are available to you for further decision making.
What will the results tell me?
All of these conditions are inherited in an autosomal recessive manner. Your test could reveal several different results:
- If both parents are carriers for the same genetic disease, then there is a 1 in 4, or 25 percent chance of the condition in each of their pregnancies. Therefore, there is a 3 in 4, or 75 percent chance that each pregnancy would be unaffected.
Prenatal diagnosis by chorionic villus sampling (CVS) at 10 to 13 weeks, or by amniocentesis at 15 to 20 weeks can diagnose these disorders. Techniques for diagnosing the disease might also be available prior to pregnancy using in vitro fertilization (IVF) and preimplantation genetic diagnosis. - When one parent is a carrier of a particular disease and the other parent is not a carrier, the couple is not at increased risk to have a child with that disease. Instead, there is a 1 in 2, or 50 percent chance of having a child who is an unaffected carrier like the one parent. Prenatal diagnosis is not recommended.
- If one parent undergoes screening initially and all the testing is negative, then no further screening or testing is recommended.
How do I arrange screening?
If you are interested in pursuing carrier screening for some or all of these conditions, please contact the Prenatal Diagnostic Center for an appointment.
Please note that medical insurance plans vary widely. Plans may cover the cost of screening at different rates. Our office can help you determine your plan's coverage and facilitate an insurance authorization if required.
Tay-Sachs disease is a genetic condition. Tay-Sachs is caused by a baby receiving two defective HEXA genes, one from each parent. Tay-Sachs disease symptoms include failing to meet motor milestones, such as sitting and standing. Babies born with Tay-Sachs often die at a young age. Genetic testing can help you make family planning decisions.
Tay-Sachs disease affects the nerve cells in the brain and spinal cord. Babies with Tay-Sachs lack a particular enzyme, which is a protein that triggers chemical reactions in cells. The lack of the enzyme, hexosaminidase A, causes a fatty substance to collect. The buildup of this substance, GM2 ganglioside, leads to Tay-Sachs symptoms such as muscle weakness.
Tay-Sachs is a genetic condition. It’s caused by changes in a pair of genes inherited from parents. It’s a progressive disease, meaning it gets worse over time. Children born with Tay-Sachs often die by age 4, usually from complications of pneumonia. There’s no cure, with treatment aimed at supporting the child and keeping them comfortable.
Genetic testing is available for couples who may face a higher risk for having a baby with Tay-Sachs. Genetic testing and counseling can help parents-to-be make informed decisions about family planning.
Who is at risk for Tay-Sachs?
People across racial and ethnic groups can carry a genetic change tied to Tay-Sachs disease. But it’s much more common among people of Ashkenazi (Eastern European) Jewish descent.
Other populations with higher numbers of people carrying the disease-causing genetic change include:
- French Canadians.
- Cajuns (from Louisiana).
- Old Order Amish (in Pennsylvania).
- Those with Irish ancestry. Some studies have shown that they have a 1 in 50 chance of carrying such a gene.
How common is Tay-Sachs disease?
For people not from high-risk backgrounds, around 1 in 300 people carry the genetic change (or variant gene) for Tay-Sachs. For people of Ashkenazi Jewish descent:
- About 1 in 30 people carry the variant gene.
- About 1 in 3,600 newborns is affected.
What are the forms of Tay-Sachs?
There are several forms of Tay-Sachs disease. The type a child has depends on when symptoms develop. Families usually only have one form of the disease. So if a child has infantile Tay-Sachs, it’s not likely that older siblings will develop juvenile or late-onset Tay-Sachs:
- Classic infantile Tay-Sachs: This is the most common form of Tay-Sachs. Children develop symptoms around 6 months.
- Juvenile Tay-Sachs: Children develop symptoms between ages 2 and 5. This form is very rare.
- Chronic Tay-Sachs: Children develop symptoms before age 10.
- Late-onset Tay-Sachs: Symptoms can appear during the teen years or early adulthood. They can also develop later as well. This type of the disease may not affect life expectancy. It’s also a very rare form of Tay-Sachs.
Are there similar diseases?
The symptoms and progression of Tay Sachs are like those of Sandhoff disease, another inherited condition. Sandhoff disease involves hexosaminidase A and a second enzyme, hexosaminidase B.
Tay-Sachs comes from a disease-causing variant (change) to the HEXA gene. Each baby has two copies of the HEXA gene, one from their biological father and one from their biological mother.
Tay-Sachs happens when both parents had a variant HEXA gene and passed it on. That means neither copy of the baby’s HEXA gene works well. Healthcare providers call this hexosaminidase A deficiency, or hex A deficiency.
What does it mean to be a Tay-Sachs carrier?
A carrier has one working copy of the HEXA gene and one copy with a disease-causing variant. Carriers don’t have the disease or show symptoms, since their bodies can rely on the working gene. But if two carriers have children together, there’s a:
- 25% (1 in 4) chance that the child won’t inherit any variant HEXA genes. The child won’t have Tay-Sachs or be a carrier.
- 50% (1 in 2) chance that the child gets a variant gene from one parent. When this happens, the child will be a carrier but won’t have Tay-Sachs. Since they’re a carrier, they may pass it to their children.
- 25% (1 in 4) chance that the child gets a variant gene from both parents. In this case, the child has Tay-Sachs disease.
What are typical symptoms of Tay-Sachs disease?
Symptoms of the most common form of Tay-Sachs start developing when babies are around 3 to 6 months old. The symptoms continue to progress as the child gets older. Children often don’t meet their developmental milestones.
Symptoms at 3 to 6 months:
- Increased startle response.
- Low muscle tone.
- Muscle weakness.
- Sudden contractions of large muscles when falling asleep, called myoclonic jerks.
Symptoms at 6 to 10 months:
- Decreased eye movement and eye contact.
- Lack of attentiveness.
- Losing ability to do tasks they could do before, such as sitting.
- Not meeting motor milestones (sitting up on their own, pulling up to standing, picking up objects with all their fingers).
- Cherry-red spot in the eye, which providers can see during an eye exam.
Symptoms at 8 to 10 months:
- Less movement.
- Less responsiveness.
- Loss of vision.
- Start of seizures.
At around a year and a half (18 months), the child’s head size starts to grow. When they’re 2 years old, they often have trouble swallowing. They may end up in an unresponsive state. This means they don’t have much brain function. Age of death is usually between 2 and 4 years old. Pneumonia is often the cause of death.
How do other forms of Tay-Sachs progress?
Less often, someone may have another form of Tay-Sachs, also caused by a hexosaminidase A deficiency. These other forms progress differently and may include additional symptoms:
Juvenile hexosaminidase A deficiency:
- Symptoms develop later than classic infantile Tay-Sachs, usually after age 2.
- Children have ataxia (trouble walking) and lack of coordination.
- Other symptoms are like classic Tay-Sachs, though the cherry-red spot in the eye is less common.
- Children may live to the teenage years.
Chronic hexosaminidase A deficiency:
- This condition usually develops before age 10.
- Children don’t lose as many motor skills as with classic Tay-Sachs.
- It affects cognitive and verbal skills later in the course of the disease.
- Children may live to their late teenage years.
Late-onset hexosaminidase A deficiency:
- People with this condition experience slow but progressive muscle weakness and wasting.
- They may also have trouble speaking clearly, problems with thinking, memory and concentration, and dementia.
- Up to 40% of people have psychiatric problems, even if they don’t have dementia.
- Life expectancy varies widely. Some people live a typical life span.
To diagnose Tay-Sachs disease, healthcare providers do a blood test. They measure the level of hexosaminidase A in the body. In a child with classic Tay-Sachs, this protein is mostly or completely missing. People with other forms of the disease have reduced levels.
A provider may also do an eye exam to see if the child has the classic cherry-red spot in the eye.
How can genetic counseling help families at risk for Tay-Sachs disease?
Genetic counseling is available for:
- Parents and relatives of children with Tay-Sachs.
- People concerned they may be Tay-Sachs carriers because of their ethnicity.
How genetic counseling works:
- A genetic counselor explains the screening options (tests that can tell if you’re a carrier).
- You undergo testing, which often includes a blood draw.
- Your genetic counselor interprets and discusses the results with you. The counselor helps you understand what the results mean for you and your family. They can also guide you through any decisions you may need to make.
You can also talk to your provider about:
- Prenatal diagnosis: Tests such as chorionic villus sampling (placental sampling) and amniocentesis (amniotic fluid sampling) can diagnose Tay-Sachs in babies before they’re born.
- Preimplantation genetic diagnosis: Specialists perform tests on embryos before implanting (placing) them in the womb. They do this to see if the embryos carry Tay-Sachs.
When should I do genetic testing for Tay-Sachs?
The best time to do genetic counseling and testing is before pregnancy. That way, you’ll have all the information you need to make the best decisions for you and your family.
There’s no cure for Tay-Sachs disease. Treatment options aim to control some of the symptoms. For example, your provider may prescribe medication to control seizures. Other treatment measures include providing proper nutrition and hydration. Children are also made as comfortable as possible. Researchers continue to explore more care options.
There’s no way to prevent Tay-Sachs disease. It’s an inherited condition. Children get it from receiving two variant genes from their parents. The best way to prevent Tay-Sachs is to have genetic testing before getting pregnant. Preconception counseling with your healthcare provider can help you plan for a future pregnancy.
Most forms of Tay-Sachs disease are fatal. Children with Tay-Sachs often pass away by age 5. Your child’s care team will talk to you about end-of-life issues. They’ll walk you through decisions about how and where you’d like your child to receive care. They’ll also discuss what you’d prefer to do if your child’s lungs stop working.
The best way to care for your child is to manage their symptoms and keep them comfortable. Your care team will work with you on:
- Breathing help: Many children with Tay-Sachs have breathing problems. They may develop lung infections because they have too much saliva and difficulty swallowing. Different medications, devices or body positioning can help your child breathe easier.
- Nutrition: A speech-language pathologist can help your child learn techniques to eat and drink. As swallowing gets worse, your child may need a feeding tube.
- Seizure control: A neurologist can help you find the right treatment plan for controlling seizures.
- Sensory stimulation: Children with Tay-Sachs have some sensory problems (issues with their five senses). You can try music, shiny mobiles, relaxing scents and soft materials to help stimulate their senses.
When should I see my healthcare provider?
Talk to your provider if:
- You’re planning a pregnancy: If you’re thinking about getting pregnant and are at high risk for Tay-Sachs disease, talk to your provider. High risk can mean you are of Ashkenazi Jewish background. It can also mean you or your partner have a history of Tay-Sachs in your families, or one or both of you is a Tay-Sachs carrier.
- You have concerns during pregnancy: If you’re pregnant and think your baby may have Tay-Sachs, reach out to a provider.
- You notice symptoms in your child: If you’re worried your child is showing Tay-Sachs symptoms, such as not reaching milestones on time, talk to your child’s provider.
What else should I ask my healthcare provider?
If you’re at high risk for having a baby with Tay-Sachs, ask your provider:
- What are my chances of having a baby with Tay-Sachs?
- Should I do genetic testing?
- How else can I lower my risk for having a baby with Tay-Sachs?
- What if my partner and I are both carriers?
- Are there treatments available for babies born with Tay-Sachs?
A note from Cleveland Clinic
Tay-Sachs disease is a rare genetic condition. It happens when each biological parent passes down a variant HEXA gene to a child. It’s more common among people from certain backgrounds, such as Ashkenazi Jewish people. Tay-Sachs disease symptoms include muscle weakness. Children also miss motor milestones, such as not pulling up to standing. There’s no cure for Tay-Sachs disease. Treatment seeks to improve quality of life and keep children comfortable. Most children born with Tay-Sachs pass away before their fifth birthday. Genetic testing can help you find out if you or your partner is a Tay-Sachs carrier. You can then make informed decisions about family planning. If you’re planning a pregnancy and at high risk for Tay-Sachs, talk to your healthcare provider.
Last reviewed by a Cleveland Clinic medical professional on 12/18/2020.
References
- Toro C, Shirvan L, Tifft C. HEXA Disorders. (//www.ncbi.nlm.nih.gov/books/NBK1218/) GeneReviews. Oct. 2020. Accessed on 11/18/2021.
- National Organization for Rare Disorders (NORD). Tay Sachs Disease. (//rarediseases.org/rare-diseases/tay-sachs-disease/) Accessed on 11/18/2021.
- National Tay-Sachs & Allied Diseases Association (NTSAD). Tay-Sachs Disease. (//www.ntsad.org/index.php/the-diseases/tay-sachs) Accessed on 11/18/2021.
- National Health Service. Tay-Sachs Disease. (//www.nhs.uk/conditions/tay-sachs-disease/) Accessed on 11/18/2021.
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