Carrier screening in the reproductive setting-Are there medical implications for the heterozygote?-A guide for...

Carrier screening for genetic conditions performed preconception or during pregnancy allows identification of fetal risk for inherited autosomal recessive and X-linked conditions. The goal is to identify at-risk patients/couples and offer them reproductive options such as preimplantation genetic diagnosis, prenatal testing, or targeted newborn testing. Although individuals are expected to be carriers for autosomal recessive conditions, most couples are not carriers of the same condition. The traditional understanding is that carriers do not exhibit symptoms of disease. However, recent studies have shown that there may be clinical implications for medical management of some conditions in the carrier state, especially in the obstetrical setting. One study showed that 9% of patients who underwent large carrier screening panels were carriers for a condition with clinical implications in the heterozygous state. It is estimated that 2.5% of females are heterozygous for a condition that impacts their medical management during pregnancy. Obstetric clinicians who often interpret carrier screen results must be aware of the potential clinical implications and incorporate this information into their counseling and management plans. In this review, we examined three large panethnic, commercially available carrier screening panels that collectively cover 818 genes. We found that 112 (13.7%) of the conditions have definite or strong implications in the carrier state, and another 100 (12.2%) have moderate or limited evidence of implications in the carrier state. Of the identified genes, 19 may have an impact during pregnancy. This information, if used to guide clinicians on conditions that require further counseling and evaluation, may improve outcomes when incorporated into obstetric practice.