The Genetics Center, Inc.   Address, phone, and fax
Carrier Screening for Ashkenazi Jewish Genetic diseases:

Answers for Health Professionals

Carrier screening for "Jewish" genetic disorders should be offered to every couple of Ashkenazi (European) Jewish ancestry, even if one or both are only partly of Ashkenazi ancestry.  Most cases of these rare disorders occur when there is no family history.  The American Congress of Obstetricians and Gynecologists (ACOG) recommends screening for, at a minimum, Tay-Sachs disease, Canavan disease, familial dysautonomia, and cystic fibrosis.

What  "Jewish" diseases are we talking about?
Tay-Sachs disease, Canavan disease, and familial dysautonomia are the most common neurodegenerative conditions, and none of these are treatable.  Additional disorders for which carrier screening is available include Niemann-Pick (type A) disease, Fanconi anemia (group C), Bloom syndrome, Gaucher disease (the non-neuronopathic type), mucolipidosis type IV, maple syrup urine disease, lipoamide dehydrogenase deficiency, familial hyperinsulinism, nemaline myopathy, Usher syndrome types III and IF, Joubert syndrome, Walker-Warburg syndrome, and glycogen storage disease type 1a.  Tay-Sachs disease is also found in persons of French-Canadian (Acadian) ancestry, possibly in Irish individuals, and rarely in mixed Jewish/non-Jewish couples.]  Although not strictly a disorder of European Jews, cystic fibrosis is often included in an Ashkenazi heritage screening panel, since it occurs with the same frequency in European Jews as in members of the non-Jewish Caucasian population (approximately 1/2,500).
How are these disorders inherited?
All are autosomal recessive, which means both members of a couple must be carriers (of the same disease) in order to have an affected child, in which case the risk of an affected child is 25% for each pregnancy.  Carrier frequencies in Ashkenazi Jews are 1 on 30 for Tay-Sachs disease and familial dysautonomia, 1 in 57 for Canavan disease, and 1 in 15 for Gaucher disease (which is mainly an adult-onset condition, often asymptomatic, for which treatment is available).  The other conditions are much rarer and have carrier frequencies generally less than 1 in 70 to 1 in 100.  Except for cystic fibrosis, for which the carrier frequency in Jews and non-Jewish Caucasians is equal, the carrier frequency for non-Jews is probably 10-fold lower for all the disorders listed above.  Sephardic and Oriental/Mizrahi Jews (i.e., Jews of Portuguese/Spanish or Middle Eastern ancestry) are at no, or at most minimally, increased risk for these disorders of Ashkenazi Jews.
How do these conditions present?
Tay-Sachs, Canavan, and Niemann-Pick disease are neurodegenerative disorders.  Onset is usually in infancy or childhood, and most affected individuals ultimately reach a vegetative state prior to demise.  Growth and development is typically normal until signs of neurodegeneration develop.  Individuals with Bloom syndrome and Fanconi anemia have growth problems and have a predisposition to early death from cancer.  Fanconi anemia, unlike Bloom syndrome, also involves cognitive impairment, and Bloom syndrome patients have immune deficiency.  Familial dysautonomia can be very difficult to diagnose and may result in sudden death in infancy or childhood before being diagnosed.  The main problems in familial dysautonomia include abnormal temperature and blood pressure regulation, abnormal sweating, insensitivity to pain, and feeding difficulties in infancy.  The non-neuronopathic type of Gaucher disease may cause anemia, splenomegaly, and bony lesions in adults.  However, no neurologic or cognitive impairment is present, and Gaucher disease can often be asymptomatic or minimally symptomatic.  Glycogen storage disease and mucolipidosis IV are lysosomal storage diseases.  Usher syndrome is a combination of retinitis pigmentosa and hearing loss.  Maple syrup urine disease and lipoamide dehydrogenase deficiency are disorders of intermediate amino acid metabolism.  Joubert and Walker-Warburg syndromes are multiple malformation syndromes with severe cranial abnormalities.
To whom should I offer screening, and for which conditions?
Cystic fibrosis carrier testing should be offered to all pregnant patients or as pre-conception screening for couples planning a pregnancy.  Either partner can be tested prior to the first trimester, whereas couple screening may be of benefit when a patient is further advanced in pregnancy, so as to permit timely prenatal diagnosis when indicated.  Carrier screening is available for individual "Ashkenazi" diseases, or, more conveniently as a panel of up to 17 Ashkenazi diseases.  Most pan-ethnic screening panels include a number of "Ashkenazi" diseases, and all include Tay-Sachs disease, Canavan disease, and familial dysautonomia.  Some authorities recommend, in addition to molecular testing for Tay-Sachs disease, enzyme-based testing, particularly for individuals with non-Ashkenazi  ancestry.  Because Ashkenazi diseases other than Tay-Sachs disease are extremely rare in non-Ashkenazi Jews, carrier screening when one member of the couple has no Ashkenazi ancestry is of minimal benefit.
What else?