Testing curbs some genetic diseases

Some of mankind's most devastating inherited diseases appear to be declining, and a few have nearly disappeared, because more people are using genetic testing to decide whether to have children.

Births of babies with cystic fibrosis, Tay-Sachs and other less-familiar disorders have dropped since testing came into wider use, according to interviews with geneticists and other experts and a review of the limited research available.

Many of the diseases are little known, and few statistics are kept. But their effects — ranging from blood disorders to muscle decline — can be disabling and often fatal during childhood.

More women now are being tested as part of routine prenatal care, and many end pregnancies when diseases are found. One study in California found that prenatal screening reduced by half the number of babies born with the severest form of cystic fibrosis, because many parents chose abortion.

More couples with no family history of inherited diseases are having tests before starting families, to see if they carry mutations that put a baby at risk. And a growing number are screening embryos and using only those without problem genes.

The cost of testing is falling, and the number of companies offering it is rising. A 2008 federal law banning gene-based discrimination by insurers and employers has eased fears.

Genetic testing pushes hot-button issues: abortion, embryo destruction and worries about eugenics — selective breeding to rid a population of unwanted traits. Yet, it is touching a growing number of people:

• In suburban Cleveland, Beth and Thad Meese were stunned to learn during her second pregnancy that they carry genes that can cause cystic fibrosis. Tests show the baby won't have the disease, but they have decided against having a third child or to screen embryos if they do. "I feel like we got lucky," she said.

• In Vancouver, B.C., Jeff and Megan Carroll screened embryos to have two children free of the Huntington's disease gene carried by Jeff. "I felt very strongly that I didn't want to pass on this," he said. Huntington's "is done killing people in my family when I am gone."

Although genetic testing for Huntington's has been important to some like the Carrolls, its impact has been less than that of testing for some other disorders.

While genetic testing can raise moral dilemmas, at least one conservative religious group — Orthodox Jews — has found ethically acceptable ways to use it.

"I am a Holocaust survivor. I was born in the middle of the second World War. I hope that I am not a suspect for practicing eugenics. We are trying to have healthy children," said Rabbi Josef Ekstein, of New York, who founded a group that tests couples and discourages matches when both carry problem genes.

Some diseases — sickle cell, cystic fibrosis, Tay-Sachs, thalassemia, spinal muscle atrophy — occur when people inherit two bad genes, one from each parent. The genes can pass quietly for generations until two carriers mate; their children then have a one-in-four chance of getting the disease.

(Down syndrome is the best-known disorder for which prenatal testing has long been available, but it's caused by an extra chromosome during abnormal cell division — not genes inherited from the parents.)

Statistics for inherited diseases are hard to come by. Birth certificates often don't list them, and they sometimes aren't diagnosed for months or years. Yet, there's little doubt that testing has put a dent in many.

"We're definitely seeing decreased rates of certain genetic disorders as a result of carrier screening," said Dr. Wendy Chung, clinical genetics chief at Columbia University. In five years, she has seen one case of Tay-Sachs, a neurological disease once more common in Eastern European Jews. Children with the disease lack a key enzyme; they lose mental and physical abilities and usually die by age 4.

Testing's dramatic effect

Lots of eyes are on cystic fibrosis, a disease that causes sticky mucus buildup in the lungs, digestive problems and death in young adulthood. More than 10 million Americans — one in 25 to 29 whites, who are more at risk than blacks — carry a gene mutation for it. The American College of Obstetricians and Gynecologists and other groups recommended in 2001 that white pregnant women be offered testing for mutations.

The impact showed up two years later in Massachusetts, one of the few states testing newborns for the disease at the time. Births of babies with cystic fibrosis dropped from 29 in 2000 to 10 in 2003, ticking up to 15 in 2006, said Dr. Richard Parad, a Brigham and Women's Hospital physician who helped set up the screening program.

In California, Kaiser Permanente offered prenatal screening. From 2006 through 2008, 87 couples with cystic-fibrosis mutations agreed to have fetuses tested, and 23 were found to have the disease. Sixteen of the 17 fetuses projected to have the severest type of disease were aborted, as were four of six fetuses projected to have less-severe disease.

Comparisons to couples not given prenatal screening suggested screening had cut births of babies with severe disease in half, researchers reported in 2008. Studies in Canada, Italy and Australia also showed drops.

The Cystic Fibrosis Foundation registry, which tracks voluntarily reported cases, shows a steady rise in recent years. But more states have started testing all newborns, discovering cases that previously would have gone unreported, some researchers believe. In December, Texas became the final state to add such testing; the first reliable national estimate of cases is expected in a couple of years.

Not all diseases down

Gene testing hasn't led to declines in all diseases. Sickle cell, a blood disorder that causes anemia and pain and increases the risk of stroke, has not dropped. The disease mostly afflicts blacks.

Newborn screening is finding more sickle-cell carriers and cases, but this doesn't seem to affect parents' future family plans, said Dr. Lanetta Jordan, a Florida physician and chief medical officer of the Sickle Cell Disease Association of America.

Gene testing also has had little impact on Huntington's disease, a progressive, fatal neurological disorder. Only one bad copy of a gene is needed to cause Huntington's, and symptoms usually don't appear until middle age, after many have had children.

Fewer than 15 percent of people in families with a history of it agree to be tested, said Kimberly Quaid, an Indiana University genetics researcher. "They just prefer to live their life and hope for the best," she said.

Jeff Carroll, the Canadian who, with his wife, screened embryos because he carries the Huntington's gene, said it is "unconscionable" to procreate without taking steps to prevent passing on the disease. "Having my test result has immensely improved my life," he said. "I was able to make reproduction decisions that ended HD in my family."

Eliminating disease is a noble goal but also "should give us pause," Dr. Barron Lerner, a Columbia University medical historian, wrote recently in the New England Journal of Medicine.

"If a society is so willing to screen aggressively to find these genes and then to potentially have to abort the fetuses, what does that say about the value of the lives of those people living with the diseases?" he asked.

It's a touchy issue. The Cystic Fibrosis Foundation notes the disease varies greatly in severity, and life expectancy now is 37 years.

Some find that diseases such as familial dysautonomia and Tay-Sachs, which kill before school age, are easier cases. If one of those vanishes, "Thank God," Rabbi Ekstein said. "It gives me a very good feeling that we are a part of such lifesaving efforts."