Expanded carrier screening panels—does bigger mean better?

Prenatal carrier screening is offered for some inherited conditions based on recommendations of the American Congress of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics and Genomics (ACMG). Currently, ACOG and ACMG recommend that cystic fibrosis carrier screening be offered to all women of reproductive age and that fragile X syndrome (FXS) carrier screening be offered to women with a family history suggestive of FXS or who ask to have testing following genetic counseling (Committee Opinion 469 2010; Committee Opinion 486 2011). For individuals of Eastern European Jewish descent, ACOG recommends carrier screening for Tay-Sachs disease, Canavan disease, cystic fibrosis, and familial dysautonomia (Committee Opinion 442 2009) stating that further testing should be permitted with appropriate counseling if the patient inquires about other conditions that occur more commonly in their ethnic group. ACMG recommends general population screening for spinal muscular atrophy, though this is unsupported by ACOG (Committee Opinion 432 2009; Prior 2008). All of these conditions are inherited in an autosomal recessive fashion except for fragile X syndrome, which is X-linked. People have two copies of each autosomal gene, one inherited from each parent. Recessive conditions manifest when both copies of the same gene have a mutation or do not function normally. Carriers have one abnormal gene copy, as well as one normal copy and are asymptomatic individuals. A 25 % risk for an affected child exists when both parents are carriers, as that poses a one in four risk for a child to receive a gene mutation from both parents. It is estimated that each individual is a carrier of between zero and seven severe childhood recessive conditions, with an average of 2.8 found in one study (Bell et al. 2011). As the first condition for which ethnicity based carrier screening was offered, cystic fibrosis (CF) is the most common lifelimiting autosomal recessive condition in non-Hispanic Caucasians. The debate over general population carrier screening began in 1990 following the discovery of the gene associated with cystic fibrosis (Karem et al. 1989; Beaudet 1990; Caskey et al. 1990; Tatsugawa et al. 1994). The discovery of the gene and the subsequent development of a genetic test were considered breakthroughs in science that would presumably lead to a cure. Questions of when and to who to offer the test presented a new ethical quandary at that time. The first report regarding routine CF carrier screening recommended against offering it to pregnant women stating that it should not yet be considered standard of care (Caskey et al. 1990). With the main benefit being to provide information for reproductive decision making, the potential limitations include anxiety over residual risk, anxiety associated with carrier status, and the cost of testing a large volume of people with very little financial benefit (Beaudet 1990). This debate was largely resolved over the next 10 years by an improvement in testing that increased detection rate, thereby reducing residual risk after negative CF carrier testing. By 2001, prenatal and preconception carrier screening for CF was S. Wienke : C. Strange Division of Pulmonary & Critical Care, Medical University of South Carolina, Charleston, SC, USA