Response to ACMG guideline: Carrier screening in individuals of Ashkenazi Jewish decent

Reply to letter from Levy-Lahad et al.:

We thank the authors for their thoughtful comments and questions regarding the new American College of Medical Genetics (ACMG) guidelines “Carrier screening in individuals of Ashkenazi Jewish descent,”¹ particularly in light of the fact that they are recognized leaders in this field. First, they are correct that there are founder mutations in non-Ashkenazi Jewish (AJ) populations that are not addressed in the current ACMG guidelines. As this document was targeted to medical practice in the United States, the guidelines reflect the absence of recognized standardized panels specific to the non-AJ population in America. However, there are certainly excellent centers, particularly in Israel, that have been offering such testing in non-AJ groups. We credit the authors who highlight that the current scientific evidence substantiates the importance of targeting tests based on specific subpopulations (e.g., phenylketonuria in Yemenite Jews) as opposed to a broad “non-AJ” or “Sephardi” panel. We would expect that the topic of carrier screening in the non-AJ population will be addressed in the near future.

We also appreciate additional points raised by the authors, specifically the question of preconception or prenatal screening for Gaucher disease, which has not been universally adopted by other professional organizations. We believe the guidelines do in fact address these concerns. We refer the authors to two other important articles in the same issue. The section on Gaucher disease in “Technical Standards and Guidelines for Reproductive Screening in the Ashkenazi Jewish Population”² does discuss variability of expression, the availability of therapies, and the carrier screening controversy. The ACMG previously has had to address similar issues in the implementation of the cystic fibrosis prenatal screening program which has been successfully integrated into current practice and serves as a paradigm for such screening programs. On that basis, like cystic fibrosis, Gaucher disease does meet our requirement expressed in criterion 2a as it does indeed “carry a potential for significant morbidity and/or mortality in the homozygous or compound heterozygous state.”¹ The fact that there is therapy does not alter the above the statement. Furthermore, the advent of such medications, while a wonderful advance in medical genetics, still comes at a significant cost and lifelong commitment for the affected and their families; this burden cannot be summarily dismissed.

Beyond this, we would like to direct the authors to perhaps the most important companion document by Pletcher et al.,³ that provides a review of the conference that was cosponsored by the ACMG and Jacobi Medical Center in 2006. The audience was addressed not only by expert medical professionals, but also by community representatives who called for education and support for screening. The consortium representing the Jewish genetic disorders is comprised of the support groups who best understand what being affected with Gaucher disease really means on a very personal level. Such organizations provide the foundation for personal autonomy, lay education, dignity, and respect for affected individuals, while including funding for research leading to clinically relevant advances in medical care and ultimately to a cure. It is these stakeholders who clearly asked us as a medical community to ensure that prospective parents be given choices that were not available before the introduction of molecular screening. Although the authors suggest that such decisions should rest exclusively with the “genetics community” and professional bodies, perhaps we need to acknowledge that these decisions are in fact not medical, but rather very personal ones that may be guided in part by ethnicity and religion. Consequently, particularly in disorders where the phenotype/genotype correlations remain poor, the ACMG guidelines reflect the notion that we can and should respect individuals' background, intellect, and autonomy to make appropriate choices following professional counseling. Contrary to the authors' perception, the ACMG does not recommend testing for Gaucher disease but instead recommends that “carrier screening be offered.”¹ Declining testing would be considered a perfectly acceptable option.

We, as genetic professionals, cannot guarantee the absence of severe disease, nor will we be forced to live with the consequences of recommendations made by professional organizations. The current guideline strives to meet the challenge put forth by Professor Scriver at the above-mentioned conference where he suggested that successful population screening programs in the future will “hinge on mutual understanding and partnership with the community.”³