Carrier Screening for Genetic Disorders in Individuals of Ashkenazi Jewish Descent

Objective: To give recommendations to physicians and midwives providing pre-conception or prenatal care about carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. Options: To offer carrier screening for Tay-Sachs disease (TSD) only or to expand the screening to include other disorders known to occur with increased frequency in the Ashkenazi Jewish population. Outcomes: To offer carrier screening to the Ashkenazi Jewish population for conditions in which the benefits to the couple outweigh the risks, which include psychological distress from screening and diagnostic interventions; to minimize practice variation across Canada with respect to carrier screening in individuals of Ashkenazi Jewish descent. Evidence: The MEDLINE database was searched for relevant articles published from January 1966 to December 2004 related to carrier screening and genetic disorders in individuals of Ashkenazi Jewish descent. In addition, Canadian maternal-fetal medicine specialists and medical geneticists were surveyed to determine current practices and opinions. Values: The results of the survey and evidence collected from the MEDLINE search were reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Examination. Benefits, harms, and costs: Screening of couples of Ashkenazi Jewish descent will identify couples who have a 25% risk of having a child with a significant genetic disorder. However, the sensitivity of the tests being offered is not 100% in individuals of Ashkenazi Jewish descent and is significantly less or unknown in non-Ashkenazi Jewish individuals. Screening might identify couples where one member is a carrier and the other member is negative. Given that such a couple would be at low risk but not zero risk of having an affected child, screening might result in psychological distress, unnecessary prenatal diagnostic procedures, and possibly termination of normal pregnancies. This guideline does not include a cost analysis. [GRAPHICS] . Recommendations 1. Carrier screening for Tay-Sachs disease (II-2A), Canavan disease, and familial dysautonomia should be offered to Ashkenazi Jewish couples. (III-A) 2. Carrier screening for other disorders seen with increased frequency in Ashkenazi Jewish individuals (e.g., Bloom syndrome, Fanconi anemia, Gaucher disease, glycogen storage disease type 1a, mucolipidosis type IV, Niemann-Pick disease type 1A, cystic fibrosis) should be offered when there is a positive family history. (III-A) 3. When only one member of a couple is of Ashkenazi Jewish ancestry, screening should be offered for TSD only. (II-2A) 4. When only one member of a couple is of Ashkenazi Jewish ancestry, screening should not be offered for Canavan disease or familial dysautonomia (FD) because of a low carrier frequency and limitations of carrier screening (low detection rate in individuals of non-Ashkenazi Jewish ancestry). (III-D) 5. When both partners are carriers of the same autosomal recessive condition, they have a 25% risk of having an affected child. They should be referred for genetic counselling, either before conception or prenatally. Prenatal diagnosis would be offered and performed according to the patient's informed decision. Prenatal diagnosis would consist of DNA analysis done on cells obtained by chorionic villus sampling or amniocentesis. (II-3A) Validation: This guideline has been prepared by the Prenatal Diagnosis Committee of the CCMG and the Genetics Committee of the SOGC and approved by the Board of Directors of the CCMG and Executive Council of the SOGC.