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Diseases commonly grouped together as “Jewish Genetic Disorders” (JGDs) range in incidence from 1/900 to 1/40,000 in the Jewish community, specifically those individuals of Ashkenazi (eastern European) heritage. Although some of these disorders in isolation would be considered rare, the overall carrier rate in this population is significant, with between 1 in 4 and 1 in 5 Ashkenazi Jews carrying a mutation for any one of these disorders. Because of genetic drift in combination with historical and social factors, certain autosomal recessive disorders have been found to occur at a higher incidence (e.g., Tay-Sachs disease) or almost exclusively in this population (e.g., familial dysautonomia) whereas other disorders may be as common as in other high risk groups (e.g., cystic fibrosis). However, the commonality for JGDs is that all exhibit the founder mutation phenomenon whereby only 1–3 mutations account for the vast majority of deleterious alterations found in this specific population.
Over 30 years ago, the development of an accurate and reliable biochemical test led to a remarkably successful community carrier screening program for Tay-Sachs disease. The subsequent widespread adoption of Tay-Sachs carrier screening resulted in a significant drop in this disease among the Ashkenazi Jewish population. Today, the vast majority of children born with Tay-Sachs disease have non-Jewish parents. Advances in our understanding of the molecular biology of Tay-Sachs disease and other Jewish genetic disorders have resulted in the identification of many of the “founder” mutations present in this population (Table 1).
As technology has improved, our ability to perform carrier screening for an increasing number of disorders has likewise expanded. However, there has been debate as to which disorders should be included in preconception/prenatal carrier screening panels and what criteria should be used to determine how this selection is made. In addition, it is important to take into account the needs of the community for which screening is intended (see commentary in this issue, page 33). Although there is no definitive mechanism whereby any individual or organization can speak for a population as a whole, experience both in the United States and Israel points to overall acceptance of carrier screening in the Jewish population if done with sensitivity and respect for cultural and religious differences. Several support groups have taken it upon themselves to educate the community and professionals about the need for comprehensive testing and prevention. The ultra-orthodox Dor Yeshorim program has advocated for broad-based testing for decades and the Central Conference of American Rabbis, the rabbinic arm of the Reform Movement, North America’s largest Jewish denomination, has passed a resolution urging all Reform Rabbis to counsel prospective couples on the availability of testing. Thus, the community focus is on the accuracy of the test and its ability to prevent significant disease as opposed to “cherry picking” disorders based on overall incidence or rarity.
This document seeks to provide guidance to clinicians regarding prenatal/preconception carrier screening for Ashkenazi Jewish individuals; however, new discoveries and technological advances will inevitably result in the availability of additional tests and revised recommendations in the future.
This guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient’s record the rationale for any significant deviation from this guideline.
Approved by the Board of Directors, July 28, 2007. Go to www.geneticsinmedicine.org for a printable copy of this document.
American College of Medical Genetics, 9650 Rockville Pike, Bethesda, MD 20814-3998.