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Supplements Expanded Carrier Screening in Prenatal Care: Recent Advances and Key Considerations

A Clinician's Perspective on Expanded Carrier Screening: A Q&A With Jodi D. Hoffman, MD

Hoffman: As opposed to diagnostic testing, in which variants of uncertain significance for a gene relevant to the condition at hand are important, screening is aimed at providing clear reproductive risks for carrier couples. Only those mutations that are known to be pathogenic via literature and ACMG variant curation guidelines are reported out. Due to the historical nature of screening for Tay-Sachs via enzyme, studies are ongoing to correlate variants in the HEXA gene with enzyme activity. To date, no variants of uncertain significance have been found to result in hexosaminidase activity in the carrier range, reassuring molecular labs that DNA sequencing has as high a level of sensitivity as the traditional enzyme activity. As the hemoglobinopathies have traditionally been screened for via hemoglobin electrophoresis and now [that] these conditions are included on many expanded panels, such correlations should also be available for these conditions. By moving toward 1 test to detect carriers for conditions [that] previously required 3 separate methodologies—molecular for CF; enzyme for Tay-Sachs; electrophoresis for hemoglobinopathies—cost savings are likely. Most patients would like to know as much information as possible when planning a pregnancy, but uncertain information is not welcome by most couples.

AJMC®: How would you assess the overall significance of prenatal genetic carrier screening and the importance of access to the technology?

Hoffman: Preconception and prenatal carrier screening are important [for] providing couples with information that allows for the birth of healthy children or for the education and preparation of parents who choose to proceed with a natural pregnancy and/or continue an affected pregnancy. For those whose moral and religious values allow the use of adoption or reproductive technologies, families can avoid the pain and suffering and economic hardships of having a child with a serious genetic condition that alters quality of life and/or length of life. For those who choose to reproduce naturally, early identification of conditions for which pregnancy or neonatal management can be altered allows for improved outcomes. For instance, if a family knows that they have a 25% chance of having a child with a metabolic condition that requires restricted protein from birth, hyperammonemia, seizures, and resultant intellectual disability may be prevented [by] assuming the baby is affected until testing is completed. For a child expected to have a severe hemophilia, special care can be taken in the newborn period to prevent bleeding due to circumcision or other procedures. Overall, whether the information is used to allow for the birth of unaffected children or affected children with optimized care, the health and well-being of families are improved due to availability of carrier screening.

  1. Edward JG, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine—points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol. 2015;123(3):653-662. doi: 10.1097/AOG.0000000000000666.
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