In their conclusions, the Israeli researchers questioned the use of genetic screening for other mild hereditary conditions. (Photo courtesy Tel Aviv University)A comprehensive, first-of-its-kind study by a team of Israeli researchers has raised the issue of whether all genetic screening programs for unborn fetuses should be offered. Thirty-five years after genetic screening was first used to identify babies at risk of being born with debilitating diseases, the study of a potentially serious but treatable illness among Ashkenazi Jews questions whether such testing has gone too far.
Illustrating the complications of prenatal genetic testing, the study, published this week in the Journal of the American Medical Association, showed that some couples chose to terminate pregnancies even though the mutation carried by their fetus probably would not have resulted in serious health problems.
According to the study, one-quarter of fetuses found to have Gaucher disease were aborted over an eight-year period, even though half of all children with the metabolic disorder will never experience any symptoms, such as pain, organ enlargement and anemia. The rest can lead normal lives with treatment.
Led by Shachar Zuckerman of Hebrew University-Hadassah Medical School in Jerusalem, the study – the first to show what couples actually do when they learn their unborn child hasd such conditions – found the rate of abortions dropped sharply if the parents-to-be consulted specialist physicians.
“The interesting thing is, as a genetic community this has been going on and we haven’t looked back to see the consequences of putting these screening programs into place,” Ephrat Levy-Lahad, a geneticist at Jerusalem’s Shaare Zedek Medical Center who took part in the study told Reuters.
The researchers focused on genetic testing for Type Gaucher disease, a genetic condition whose symptoms range from severe to nonexistent. It occurs mainly in Ashkenazi Jews, or those of Eastern or Central European descent.
Gaucher disease (GD) includes three diseases that are due to deficient activity of a certain enzyme. Carrier screening for GD is controversial because common type 1 GD is often asymptomatic and is usually not severe or untreatable, and the test performed does not fully predict disease severity. The test has been offered in Israel and worldwide since 1995.
According to the US National Gaucher Foundation, the most common symptoms of the disease are enlarged livers and spleens; anemia; reduced platelets that can result in easy bruising and clotting difficulties; bone “infarctions” that can lead to damage to the shoulder or hip joints; and a generalized “demineralization” of the bones, or osteoporosis. This can lead to spontaneous fractures.
Ten Israeli genetic centers provided data on the number of individuals screened for GD, the number of carriers identified, the number of carrier couples identified, and the mutations identified in these couples between January 1995 and March 2003.
The researchers investigated found 82 “carrier couples” whose children risked being born with Type 1 GD. Three-quarters of the couples had prenatal diagnosis performed when they got pregnant, and 16 affected fetuses were identified. Four of the 16 were aborted.
The study found that there were far fewer pregnancy terminations among couples who, in addition to receiving genetic counseling, also had medical counseling with a Gaucher disease expert – one of 13 (eight percent) of pregnancies, compared with three of three (100 percent) among couples who did not receive medical counseling.
“With respect to the stated goal of carrier screening programs, the main practical outcome of GD screening was a 66 percent reduction in birth prevalence for moderate type 1 GD, for which the estimated frequency is 1 in 27,000, and a 15 percent reduction in the birth prevalence of asymptomatic or mild type 1 GD, for which the estimated frequency is 1 in 1,300. This was achieved through termination of pregnancy of fetuses either treatable or likely to be asymptomatic, and it is debatable whether this represents a true benefit,” the study authors wrote.
They noted that the Israeli Medical Geneticists Association has recommended against Gaucher disease screening.
In their conclusions, the Israeli researchers questioned the use of genetic screening for other mild hereditary conditions.
“Applying the classic carrier screening paradigm to common, low-penetrance disease leads to inevitable dilemmas, and programs offering such screening should determine whether the true goal is knowledge and presymptomatic risk assessment or pregnancy termination of fetuses with a specified genetic status,” the researchers wrote.
“Our results suggest that to avoid termination of pregnancies for generally mild conditions, even in a highly educated population, screening programs would require a combination of traditional, nondirective genetic counseling with medical counseling by professionals familiar with the specific diseases,” they concluded.
“This is a cautionary tale of the future of genetics in general,” said Levy-Lahad.
Doctors often use genetic tests to screen for diseases such as cystic fibrosis to allow parents to end a pregnancy that would lead to a severely disabled child. But the issue is far less clear when it comes to conditions like Gaucher disease and raises the question if tests for much less severe diseases should be given, Levy-Lahad said.