HEALTH Taking a Chance on Life

Predicting the future has become easier; dealing with it hasn’t.

By the time Jeffrey Pearson was six weeks old, his mother knew something was wrong. “I could tell he wasn’t opening his eyes fully,” says Pat Pearson. “We took him to the pediatrician, and he said some of the muscles around Jeffrey’s eyes were paralyzed and that he had strabismus [difficulty controlling eye movements]. After that we were in and out of the doctor’s office quite a bit, and we found out he had a heart problem. Then we found out his major pectoralis muscles were absent. That means he doesn’t have much strength in his hands or arms.”

Jeffrey was born in 1972. Now Pat Pearson sits in the kitchen of their house in Richardson; they had moved in two weeks before Jeffrey was born. Her other son, Michael, a normal and very active 18-month-old, runs through the kitchen, stopping to eye the bag of Oreos on the table. Jeffrey is at school.

“He just started this spring; he still hasn’t started to talk. We had been told he was severely retarded. But we found out last year that a big part of his problem is that he’s almost totally deaf; he just got a hearing aid. Now he’s in a mainstreaming program, going to a special wing of a regular elementary school.

“Jeffrey’s had other troubles: He had kidney failure two years ago; we still don’t know why. And when he was three-and-a-half he started walking and broke his foot right away. But he’s a neat kid; I’m proud to be his mother.”

When Mrs. Pearson and her husband, Jimmy, a computer programmer, learned of Jeffrey’s problems, they began to worry about the risk that they might have more children with the same condition. In October 1972, an ophthalmologist suggested they take Jeffrey to the genetic counseling clinic that had just opened at the Children’s Medical Center. Jeffrey’s condition had already been diagnosed as a rare neurological disorder, Mobius syndrome. In the absence of more information, the doctors at the clinic told her that the chances for recurrence in her family were about the same as those for more common birth defects – about five percent. With those odds, the Pearsons didn’t worry too much when Pat became pregnant with Michael.

The five-percent estimate had to be revised four months ago, however, when Pat Pearson cleaned out the attic in her mother’s house. “I found a family photo album going back four generations,” she says, “and in almost every generation there were one or two with sleepy-looking eyes like Jeffrey’s.” She took the album to Drs. Mary Jo Harrod and Jan Friedman at the genetic counseling clinic, which had moved from Children’s Medical Center to the UT Health Science Center in May. Harrod has been with the clinic since 1972; Friedman came to Dallas last April. “They were tremendously excited by the book,” says Mrs. Pearson. The fact that so many of her ancestors looked sleepy-eyed indicated that the probability of inheritance was considerably greater than five percent; Jeffrey’s disorder, which had seemed to be an unlucky chance occurrence, now appeared as part of a pattern.

With the subject re-opened, Pat Pearson hesitantly told Harrod and Friedman about some neurological problems of her own. “My mother and I both have trouble hearing sometimes; we can hear, but the words don’t make sense.. And we occasionally have dizzy spells – not really dizzy, but feeling like you’re about to fall. I’d been to two doctors about my hearing problem, but they didn’t say much; one insinuated that it was all in my mind.”

After hearing her story and drawing a chart showing the pattern of inheritance for “sleepy eyes,” Friedman and Harrod concluded that it is likely that at least some of Jeffrey’s difficulties are caused by a single gene – the same one that gives his mother and grandmother dizzy spells. It’s not clear why Jeffrey is so much more severely affected than his mother; there may be other genes which influence how strongly the deleterious gene is expressed.

This carries some serious implications for Jeffrey’s brother and older sister. There is a chance that they carry the deleterious gene but are affected only mildly, as is their mother. Should they develop dizzy spells in the future, they will have to keep in mind the possibility that one of their children will have a condition like Jeffrey’s.

Of the 15,000 babies born in Dallas last year, about 750 suffer from birth defects, including retardation, malformation, and metabolic disorders. Chromosomal abnormalities are found in half of all spontaneously aborted fetuses and in about five percent of the stillbirths and infants dying within a week of birth. Twelve percent of all children admitted to hospitals in the U.S. suffer from diseases that are, at least in part, genetic in origin. Seventeen percent are congenitally malformed.

Genetic defects cannot be cured, because chromosomes cannot be reconstructed. Though some disorders can be treated, affected individuals face lifelong medical problems. “We’re here to help people make informed decisions,” says Dr. Friedman. “We diagnose genetic disorders and provide people who are at risk with the information they need to make intelligent decisions about having children.” He and Dr. Harrod share a small office on the fourth floor of a research building on the Health Science Center campus. The walls are lined with books and journals. There isn’t a Bunsen burner or mysterious-looking piece of glassware in sight. Most of the business of genetic counseling is conducted with pencil and paper. “What we do most of the time,” says Harrod, “is take family histories and estimate a couple’s chance of having affected children. We always try to be non-directive: We present the facts, they make the decision.” The decisions are difficult: whether or not to conceive a child which will have a 25-percent chance of being born with cystic fibrosis; whether or not to abort a fetus with Down syndrome.

Harrod and Friedman and their associates talk with an average of 15 couples every week. Most of them have had one child with a congenital defect, such as open spine or cleft palate, and are worried that future children will be similarly affected. Such couples run about a five-percent risk with each pregnancy.

Others have histories of hereditary diseases in their families or are members of ethnic groups with a high rate of a particular disease – sickle cell anemia, for example, which affects 1 in 400 black Americans; or Tay-Sachs disease, affecting 1 in 2500 Jews of East European origin. In some of these cases, a simple lab test can determine a couple’s risk of having an affected child.

Women over 35 constitute the largest group at risk; as a woman ages, she runs an increasing risk of having a child with Down syndrome (which used to be called Mongolism). Down syndrome can be diagnosed by amniocentesis, a technique for looking at fetal cells, as can some birth defects and hereditary diseases.

Inside almost every cell of everyone’s body there are 46 chromosomes. Each chromosome contains hundreds of genes; each gene contains the pattern according to which a protein is made. Proteins control all the chemical reactions that add up to life.

The genetic information in each cell is redundant; 23 of the chromosomes are copies of the father’s, and 23 copies of the mother’s. Each set of 23 contains all the genes necessary to make all the body’s proteins. Everyone carries two genes for each protein; but a pair of genes that code for the same protein are often not exactly the same. The variations in protein structure that result from variations in genes is the source of differences between individuals. Most visible traits are due to the interaction of many genes, but some visible traits are governed by single genes. The most familiar example is eye color. To keep it simple, consider just the genes for blue and brown: If a person carries two blue genes, his eyes are blue; if he has two browns or a blue and a brown, they’re brown. (In the real world, blue-eyed parents often have brown-eyed children because more than one gene is involved.) Since a parent gives only one member of each pair of similar genes to his. child, brown-eyed parents who both carry genes for blue and brown eyes can have a blue-eyed child – the likelihood is 25 percent. Because the brown gene is expressed even in the presence of the blue, it is called dominant; the blue gene, which must be present in two copies to be expressed, is recessive.

Like eye color in the example above, more than 2000 genetic disorders are known to be controlled by single genes. About half, including sickle cell, Tay-Sachs, and cystic fibrosis, are recessive, like blue eyes. A person may carry one gene for any of these disorders and be perfectly healthy; but if his mate also carries a single copy of the gene, each of their children has a 25-percent chance of being affected. The genes for Tay-Sachs, sickle cell, and some other recessive disorders can be detected in unaffected carriers by simple biochemical tests for the proteins involved. But most single-gene disorders can be identified only by their symptoms; risk can be assessed only on the basis of family history. Cystic fibrosis, for example, strikes 1 in 1600 whites; that’s the probability that a couple with no history of the disease on either side will have an affected child. If husband or wife has a sibling with cystic fibrosis, the chance is 1 in 120; if both have affected siblings, the chance is 1 in 9; if they have one affected child, the risk for every subsequent child is 1 in 4.

Half the known single-gene disorders are dominant. Jeffrey Pearson’s neurological problem and Huntington’s chorea fall in this category. In dominant disorders, all carriers (and only carriers) are affected, whether they carry one copy of the deleterious gene or two. Huntington’s chorea and many other dominant diseases manifest themselves only after the affected person has reached reproductive age.

When most people hear “genetic defect,” they think of congenital malformations such as open spine, clubfoot, and cleft palate. These defects are caused by a complex of genetic and environmental factors, so they are called multifactorial. There is no strict inheritance pattern, as there is for single-gene defects, but some families are more likely to have malformed children than others. (Other diseases follow the same pattern: high blood pressure, for example.) The risks for congenital malformations are based on birth statistics; a couple that has had one child with a birth defect runs about a five-percent risk with each subsequent child.

Single-gene and multifactorial disorders are detected indirectly by their effects, but a third kind of genetic defect can be seen directly under the microscope: chromosomal abnormalities. Individuals with these abnormalities don’t have 46 chromosomes; they may have more or fewer, or be missing part of a single chromosome. The most familiar example is Down syndrome.

After age 35, a woman runs a 1-in-80 risk of conceiving a child with 47 chromosomes instead of 46, the extra being a third copy of the one designated number 21; her risk increases every year. (The risk for women under 30 is less than 1 in 1000.) A person with three copies of number 21 has Down syndrome, whose principal effect is severe retardation. (Men over age 50 are at risk, too, but not for Down syndrome. Their children are more likely than the children of younger men to carry new dominant mutations. The possibilities for such mutations are so numerous that it would be impossible to screen them before birth.)

Down syndrome and other chromosomal abnormalities, open spine, and about 60 single-gene defects can be detected at the end of the fourth month of pregnancy by amniocentesis.When the fetus is 14 weeks old, a needle is inserted into the mother’s uterus and used to draw off some of the amniotic fluid. This fluid contains skin cells sloughed off by the fetus; the cells are placed in a nutrient bath, where they grow and divide. They can then be examined under the microscope or analyzed biochemically. In the 10 years since the technique was developed, amni-ocentesis has changed the nature of genetic counseling. Before prenatal diagnosis, couples could learn only the probability they faced of having affected children; if the risk was high, they could choose to adopt children, and conceive none of their own. Now, for an ever-increasing number of disorders, diagnosis is a fact, not a probability. The reassurance given by a favorable diagnosis is immense. But there must be a fetus to be diagnosed: A woman who learns she carries a defective fetus must choose between abortion and bearing a child with serious medical problems.

Genetic counselors say they provide information, not advice. But the problems they deal with are serious, and the solutions are drastic. It is essential that a woman understand that amniocentesis may tell her she is carrying a defective child. And there may be a risk to the fetus in amniocentesis. A study of a thousand tests in 1972 showed no more miscarriages or birth defects than in the control group. But the oldest child to have been tested this way is still only six years old; it cannot be categorically stated that there is no risk involved in this procedure.

Like all tests, amniocentesis is subject to error, though errors are very rare. In the study mentioned above, 99.4 percent of the diagnoses were correct. The odds are a little worse in the test for open spine; according to Friedman, 1 to 2 percent of the results are false-positives – a normal fetus is diagnosed as defective. As Friedman points out, this percentage is very small compared to the death rate among children with open spine. But a pregnant woman isn’t thinking about 99 percent of the cases; she’s thinking about the child she carries.

Sometimes amniocentesis yields ambiguous results. Says Friedman, “Once in a while we perform amniocentesis on a 40-year-old woman, make several separate cell cultures, and in just one of the cultures pick up cells with abnormal chromosomes. It may be the fetus has some normal cells and some abnormal ones, in which case it would almost certainly have problems; or, it may be that the abnormality developed while the cells were in culture – that’s known to happen. Unfortunately, we can’t do another test at this point, because the pregnancy is too far along. So we have to just let the woman know all the possibilities. Obviously we haven’t put her mind at ease.”

The most painful decisions are forced by disorders that generate severe problems, but are not fatal or crippling. A case in point is Klinefelter’s syndrome, a chromosome abnormality that can be detected by amniocentesis. Affected individuals are males with some feminine characteristics, which can be counteracted by hormone treatments; they are often mentally retarded. But some apparently normal men of normal intelligence carry the same chromosome abnormality. How does one weigh the probability of retardation against the finality of abortion?

At the UT Health Science Center, am-niocenteses are performed on an averageof four women a week; about half areover 35, most of the rest have had onechild with a genetic disorder, and a feware known or likely carriers of deleteriousgenes. In the 300 tests performed so far,293 women have learned that the fetusesthey carried had no detectable abnormalities; many of them, facing a high riskof bearing a defective child, would havechosen abortion without this reassurance.Seven women were found to carry fetuseswith chromosomal abnormalities; all seven chose abortion.


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